rs9324685

Variant names:

• chr5-151267479-C-T
• rs9324685
• NM_000405.5:c.*28C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-151267479-C-T
• chr5-151267479-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000405.5(GM2A):​c.*28C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,613,684 control chromosomes in the GnomAD database, including 4,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (1089 hom., cov: 32)
  • Exomes 𝑓: 0.046 (3264 hom.)
• Consequence: GM2A NM_000405.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35
• Publications: 8 publications found

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]

GM2A Gene-Disease associations (from GenCC):

• Tay-Sachs disease AB variant

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-151267479-C-T is Benign according to our data. Variant chr5-151267479-C-T is described in ClinVar as Benign. ClinVar VariationId is 256029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000405.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GM2A	NM_000405.5	MANE Select	c.*28C>T		3_prime_UTR	Exon 4 of 4	NP_000396.2
	GM2A	NM_001167607.3		c.413-13C>T		intron	N/A	NP_001161079.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GM2A	ENST00000357164.4	TSL:1 MANE Select	c.*28C>T		3_prime_UTR	Exon 4 of 4	ENSP00000349687.3	P17900
	GM2A	ENST00000937902.1		c.*28C>T		3_prime_UTR	Exon 3 of 3	ENSP00000607961.1
	GM2A	ENST00000523004.1	TSL:1	c.*554C>T		downstream_gene	N/A	ENSP00000430541.1	H0YBY3

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13508 AN: 152092 Hom.: 1086 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0699

GnomAD2 exomes AF: 0.0716 AC: 17956 AN: 250922 AF XY: 0.0684

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0705

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.0441

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0455 AC: 66567 AN: 1461474 Hom.: 3264 Cov.: 34 AF XY: 0.0460 AC XY: 33477 AN XY: 727046

African (AFR) AF: 0.198 AC: 6627 AN: 33450

American (AMR) AF: 0.0692 AC: 3093 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 755 AN: 26130

East Asian (EAS) AF: 0.250 AC: 9934 AN: 39690

South Asian (SAS) AF: 0.0854 AC: 7360 AN: 86216

European-Finnish (FIN) AF: 0.0439 AC: 2340 AN: 53360

Middle Eastern (MID) AF: 0.0309 AC: 178 AN: 5768

European-Non Finnish (NFE) AF: 0.0292 AC: 32477 AN: 1111784

Other (OTH) AF: 0.0630 AC: 3803 AN: 60382

GnomAD4 genome AF: 0.0889 AC: 13528 AN: 152210 Hom.: 1089 Cov.: 32 AF XY: 0.0908 AC XY: 6759 AN XY: 74412

African (AFR) AF: 0.193 AC: 8003 AN: 41524

American (AMR) AF: 0.0680 AC: 1041 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0276 AC: 96 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1334 AN: 5156

South Asian (SAS) AF: 0.0967 AC: 466 AN: 4820

European-Finnish (FIN) AF: 0.0398 AC: 422 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0294 AC: 1997 AN: 68020

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0553 Hom.: 170

Bravo AF: 0.0954

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Tay-Sachs disease, variant AB (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.44
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9324685; hg19: chr5-150647040; COSMIC: COSV64095301; COSMIC: COSV64095301;