rs153462

Positions:

• 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]

(HGNC:):

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/exons	MANE	Protein	UniProt
		n.151225509A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000523466.5	c.126+12620A>G		intron_variant		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;