NM_014363.6(SACS):c.6155C>G (p.Ser2052Ter) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 14, 2023
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:: RCV004447324.1

Allele description [Variation Report for NM_014363.6(SACS):c.6155C>G (p.Ser2052Ter)]

NM_014363.6(SACS):c.6155C>G (p.Ser2052Ter)

Gene:

SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.6155C>G (p.Ser2052Ter)

HGVS:

NC_000013.11:g.23337721G>C
NG_012342.1:g.100982C>G
NM_001278055.2:c.5714C>G
NM_014363.6:c.6155C>GMANE SELECT
NP_001264984.1:p.Ser1905Ter
NP_055178.3:p.Ser2052Ter
NC_000013.10:g.23911860G>C
NM_014363.4:c.6155C>G

Protein change:

S1905*

Molecular consequence:

NM_001278055.2:c.5714C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_014363.6:c.6155C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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
SCV004943968	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 14, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004943968

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 14, 2023)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV004943968.1

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

Description

The c.6155C>G (p.S2052*) alteration, located in exon 10 (coding exon 9) of the SACS gene, consists of a C to G substitution at nucleotide position 6155. This changes the amino acid from a serine (S) to a stop codon at amino acid position 2052. This alteration occurs at the 3' terminus of the SACS gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 55% of the protein. Premature stop codons are typically deleterious in nature, the impacted region is critical for protein function, and a significant portion of the protein is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.

#	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: May 7, 2024

ClinVar

Relating variation to medicine