NM_015909.4(NBAS):c.2951T>G (p.Ile984Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001885311.5

Allele description [Variation Report for NM_015909.4(NBAS):c.2951T>G (p.Ile984Ser)]

NM_015909.4(NBAS):c.2951T>G (p.Ile984Ser)

Gene:

NBAS:NBAS subunit of NRZ tethering complex [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p24.3

Genomic location:

Preferred name:

NM_015909.4(NBAS):c.2951T>G (p.Ile984Ser)

HGVS:

NC_000002.12:g.15402288A>C
NG_032964.1:g.164061T>G
NM_015909.4:c.2951T>GMANE SELECT
NP_056993.2:p.Ile984Ser
NC_000002.11:g.15542412A>C
NM_015909.3:c.2951T>G
NR_052013.3:n.2981T>G

Protein change:

I984S

Links:

dbSNP: rs140841721

NCBI 1000 Genomes Browser:

rs140841721

Molecular consequence:

NM_015909.4:c.2951T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_052013.3:n.2981T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236519	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26073778, 31761904, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236519

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy.

Haack TB, Staufner C, Köpke MG, Straub BK, Kölker S, Thiel C, Freisinger P, Baric I, McKiernan PJ, Dikow N, Harting I, Beisse F, Burgard P, Kotzaeridou U, Kühr J, Himbert U, Taylor RW, Distelmaier F, Vockley J, Ghaloul-Gonzalez L, Zschocke J, Kremer LS, et al.

Am J Hum Genet. 2015 Jul 2;97(1):163-9. doi: 10.1016/j.ajhg.2015.05.009. Epub 2015 Jun 11.

PubMed [citation]

PMID:: 26073778
PMCID:: PMC4572578

Defining clinical subgroups and genotype-phenotype correlations in NBAS-associated disease across 110 patients.

Staufner C, Peters B, Wagner M, Alameer S, Barić I, Broué P, Bulut D, Church JA, Crushell E, Dalgıç B, Das AM, Dick A, Dikow N, Dionisi-Vici C, Distelmaier F, Bozbulut NE, Feillet F, Gonzales E, Hadzic N, Hauck F, Hegarty R, Hempel M, et al.

Genet Med. 2020 Mar;22(3):610-621. doi: 10.1038/s41436-019-0698-4. Epub 2019 Nov 25.

PubMed [citation]

PMID:: 31761904

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002236519.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 984 of the NBAS protein (p.Ile984Ser). This variant is present in population databases (rs140841721, gnomAD 0.003%). This missense change has been observed in individual(s) with SOPH syndrome and acute liver failure (PMID: 26073778, 31761904). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1335897). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 24, 2023

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