rs153462

Variant names:

• chr5-151225509-A-G
• rs153462
• ENST00000523466.5:c.126+12620A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-151225509-A-G
• chr5-151225509-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523466.5(GM2A):​c.126+12620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,088 control chromosomes in the GnomAD database, including 6,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6118 hom., cov: 32)
• Consequence: GM2A ENST00000523466.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000523466.5	c.126+12620A>G		intron_variant	Intron 2 of 3	3		ENSP00000429100.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42524 AN: 151970 Hom.: 6119 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.280 AC: 42544 AN: 152088 Hom.: 6118 Cov.: 32 AF XY: 0.285 AC XY: 21204 AN XY: 74344

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.278

Alfa AF: 0.262 Hom.: 11587

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs153462; hg19: chr5-150605070;