NM_005360.5(MAF):c.185C>T (p.Thr62Met) AND Ayme-Gripp syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jul 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001775246.2

Allele description [Variation Report for NM_005360.5(MAF):c.185C>T (p.Thr62Met)]

NM_005360.5(MAF):c.185C>T (p.Thr62Met)

Gene:

MAF:MAF bZIP transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_005360.5(MAF):c.185C>T (p.Thr62Met)

HGVS:

NC_000016.10:g.79599718G>A
NG_016440.1:g.6008C>T
NM_001031804.3:c.185C>T
NM_005360.5:c.185C>TMANE SELECT
NP_001026974.1:p.Thr62Met
NP_005351.2:p.Thr62Met
NC_000016.9:g.79633615G>A
NM_001031804.2:c.185C>T

Protein change:

T62M

Links:

dbSNP: rs727502771

NCBI 1000 Genomes Browser:

rs727502771

Molecular consequence:

NM_001031804.3:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005360.5:c.185C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Ayme-Gripp syndrome
Identifiers:: MONDO: MONDO:0010992; MedGen: C1832812; OMIM: 601088

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002011958	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004171009	DECIPHERD-UDD, Universidad del Desarrollo	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 1, 2023)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 38177409

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002011958

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 2, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004171009

DECIPHERD-UDD, Universidad del Desarrollo

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 1, 2023)

unknown

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile.

Poli MC, Rebolledo-Jaramillo B, Lagos C, Orellana J, Moreno G, Martín LM, Encina G, Böhme D, Faundes V, Zavala MJ, Hasbún T, Fischer S, Brito F, Araya D, Lira M, de la Cruz J, Astudillo C, Lay-Son G, Cares C, Aracena M, Martin ES, Coban-Akdemir Z, et al.

Eur J Hum Genet. 2024 Jan 4. doi: 10.1038/s41431-023-01523-5. [Epub ahead of print]

PubMed [citation]

PMID:: 38177409

Details of each submission

From 3billion, SCV002011958.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Thr62Arg) has been reported as pathogenic/likely pathogenic with supporting evidence (ClinVar ID: VCV000162517.1, PM5_P). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87, 3Cnet: 0.892, PP3). Patient's phenotype is considered compatible with Ayme-Gripp syndrome (3billion dataset, PP4).Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From DECIPHERD-UDD, Universidad del Desarrollo, SCV004171009.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 10, 2024

ClinVar

Relating variation to medicine