5-151253547-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000405.5(GM2A):c.81+250C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,230 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (369 hom., cov: 32)
• Consequence: GM2A NM_000405.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507

Genes affected

GM2A (HGNC:4367): (ganglioside GM2 activator) This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-151253547-C-A is Benign according to our data. Variant chr5-151253547-C-A is described in ClinVar as [Benign]. Clinvar id is 1228124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GM2A	NM_000405.5	c.81+250C>A		intron_variant		ENST00000357164.4
GM2A	NM_001167607.3	c.81+250C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GM2A	ENST00000357164.4	c.81+250C>A		intron_variant		1	NM_000405.5	P1
GM2A	ENST00000523466.5	c.127-6208C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10707 AN: 152112 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0703 AC: 10703 AN: 152230 Hom.: 369 Cov.: 32 AF XY: 0.0699 AC XY: 5199 AN XY: 74428

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.0904

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0669

Alfa AF: 0.0400 Hom.: 37

Bravo AF: 0.0703

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41290575; hg19: chr5-150633108; COSMIC: COSV64095313;