VCV000805790.6 - ClinVar

NM_006279.5(ST3GAL3):c.1046C>T (p.Thr349Met)

Interpretation:: Likely pathogenic
Review status:: criteria provided, single submitter
Submissions:: 3
First in ClinVar:: Jan 19, 2020
Most recent Submission:: Nov 5, 2022
Last evaluated:: Feb 8, 2022
Accession:: VCV000805790.6
Variation ID:: 805790
Description:: single nucleotide variant

NM_006279.5(ST3GAL3):c.1046C>T (p.Thr349Met)

Allele ID

794110

Variant type

single nucleotide variant

Variant length

1 bp

Cytogenetic location

1p34.1

Genomic location

1: 43930139 (GRCh38) GRCh38 UCSC

1: 44395811 (GRCh37) GRCh37 UCSC

HGVS

Nucleotide	Protein	Molecular consequence
NM_006279.5:c.1046C>T MANE Select	NP_006270.1:p.Thr349Met	missense
NM_001270459.2:c.956C>T	NP_001257388.1:p.Thr319Met	missense
NM_001270460.2:c.953C>T	NP_001257389.1:p.Thr318Met	missense
NM_001270461.3:c.704C>T	NP_001257390.1:p.Thr235Met	missense
NM_001270462.3:c.611C>T	NP_001257391.1:p.Thr204Met	missense
NM_001270463.3:c.562C>T	NP_001257392.1:p.Arg188Cys	missense
NM_001270464.3:c.517C>T	NP_001257393.1:p.Arg173Cys	missense
NM_001270465.3:c.*30C>T		3 prime UTR
NM_001270466.3:c.262C>T	NP_001257395.1:p.Arg88Cys	missense
NM_001350619.2:c.1287C>T	NP_001337548.1:p.Asp429=	synonymous
NM_001350620.2:c.1242C>T	NP_001337549.1:p.Asp414=	synonymous
NM_001350621.2:c.963C>T	NP_001337550.1:p.Asp321=	synonymous
NM_001363573.2:c.914C>T	NP_001350502.1:p.Thr305Met	missense
NM_174963.5:c.1253C>T	NP_777623.2:p.Thr418Met	missense
NM_174964.4:c.1091C>T	NP_777624.1:p.Thr364Met	missense
NM_174965.4:c.450C>T	NP_777625.1:p.Asp150=	synonymous
NM_174966.4:c.752C>T	NP_777626.1:p.Thr251Met	missense
NM_174967.4:c.405C>T	NP_777627.1:p.Asp135=	synonymous
NM_174968.5:c.1208C>T	NP_777628.2:p.Thr403Met	missense
NM_174969.4:c.998C>T	NP_777629.1:p.Thr333Met	missense
NM_174970.4:c.357C>T	NP_777630.1:p.Asp119=	synonymous
NM_174971.5:c.1160C>T	NP_777631.2:p.Thr387Met	missense
NR_073016.3:n.1266C>T		non-coding transcript variant
NR_073017.3:n.1143C>T		non-coding transcript variant
NR_073018.3:n.1113C>T		non-coding transcript variant
NR_073019.3:n.1082C>T		non-coding transcript variant
NR_073020.3:n.999C>T		non-coding transcript variant
NR_073021.3:n.927C>T		non-coding transcript variant
NR_073023.3:n.887C>T		non-coding transcript variant
NR_146867.2:n.1462C>T		non-coding transcript variant
NC_000001.11:g.43930139C>T
NC_000001.10:g.44395811C>T
NG_028196.1:g.227594C>T

... more HGVS ... less HGVS

Protein change

R173C, R188C, R88C, T204M, T235M, T251M, T305M, T318M, T319M, T333M, T349M, T364M, T387M, T403M, T418M

Other names

Canonical SPDI

NC_000001.11:43930138:C:T

Functional consequence

Uncertain function

Global minor allele frequency (GMAF)

Allele frequency

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD) 0.00003

Links

OMIM: 606494.0004

dbSNP: rs1201878175

VarSome

Aggregate interpretations per condition

Interpreted condition	Interpretation	Number of submissions	Review status	Last evaluated	Variation/condition record
Aggressive behavior Difficulty walking Frequent falls Intellectual disability, severe Prolonged neonatal jaundice	Uncertain significance	1	no assertion criteria provided	-	RCV000993574.1
Intellectual disability, autosomal recessive 12	Likely pathogenic	2	criteria provided, single submitter	Feb 8, 2022	RCV001290010.6

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation viewer	Related variants
Gene	OMIM	HI score Help	TS score Help	Variation viewer	Within gene	All
ST3GAL3		-	-	GRCh38 GRCh37	318	340

Submitted interpretations and evidence

Interpretation (Last evaluated)	Review status (Assertion criteria)	Condition (Inheritance)	Submitter	More information
Likely pathogenic (Feb 08, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	- Intellectual disability, autosomal recessive 12 Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV002512706.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Comment: ACMG classification criteria: PS4 supporting, PM2 moderate, PM3 moderate, PP1 supporting, BP4 supporting Geographic origin: Brazil
Uncertain significance (-)	no assertion criteria provided Method: case-control	- Prolonged neonatal jaundice - Difficulty walking - Frequent falls - Aggressive behavior - Difficulty walking - Frequent falls - Intellectual disability, severe (Autosomal recessive inheritance) Affected status: yes Allele origin: inherited	Human Genetics Department, Tarbiat Modares University Accession: SCV001142665.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Zygosity: 1 Homozygote Age: 30-39 years Sex: female Testing laboratory: DeNA laboratory Date variant was reported to submitter: 2019-01-01 Testing laboratory interpretation: Uncertain significance
Pathogenic (Nov 02, 2022)	no assertion criteria provided Method: literature only	- INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 12 Affected status: not provided Allele origin: germline	OMIM Accession: SCV001478064.3 First in ClinVar: Jan 26, 2021 Last updated: Nov 05, 2022	Publications: PubMed (1) PubMed: 32666583 Comment on evidence: In 2 first cousins (patients V.1 and V.4) from a consanguineous Iranian family with autosomal recessive intellectual developmental disorder-12 (MRT12; 611090), Farajollahi et al. (2020) … (more) In 2 first cousins (patients V.1 and V.4) from a consanguineous Iranian family with autosomal recessive intellectual developmental disorder-12 (MRT12; 611090), Farajollahi et al. (2020) identified homozygosity for a c.704C-T transition (c.704C-T, NM_001270461.2) in a conserved region of exon 9 of the ST3GAL3 gene, resulting in a thr235-to-met (T235M) substitution. The mutation was identified by whole-exome sequencing and Sanger sequencing. Both sets of parents were mutation carriers. The variant was absent in the dbSNP, 1000 Genomes Project, Exome Sequencing Project, and ExAC databases. Molecular modeling predicted that the mutation might interfere with ligand binding and decrease protein stability. Two other family members (sibs of patient V.4) had a history of clinical features consistent with MRT12, but were deceased and not tested. (less)

Functional evidence

Functional consequence	Method	Result	Submitter	More information
Uncertain function			Human Genetics Department, Tarbiat Modares University Accession: SCV001142665.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020

Citations for this variant

Title	Author	Journal	Year	Link
A novel variant of ST3GAL3 causes non-syndromic autosomal recessive intellectual disability in Iranian patients.	Farajollahi Z	The journal of gene medicine	2020	PMID: 32666583

Text-mined citations for rs1201878175...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 06, 2023

ClinVar Genomic variation as it relates to human health

NM_006279.5(ST3GAL3):c.1046C>T (p.Thr349Met)

NM_006279.5(ST3GAL3):c.1046C>T (p.Thr349Met)

Aggregate interpretations per condition

Submitted interpretations and evidence

Functional evidence

Citations for this variant

Text-mined citations for rs1201878175...