5-151251730-A-T

Variant summary

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

The ENST00000523466.5(GM2A):c.127-8025A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,632 control chromosomes in the GnomAD database, including 28,272 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 0.60 (28272 hom., cov: 29)
• Consequence: GM2A ENST00000523466.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GM2A	ENST00000523466.5	c.127-8025A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91076 AN: 151514 Hom.: 28243 Cov.: 29

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.601 AC: 91157 AN: 151632 Hom.: 28272 Cov.: 29 AF XY: 0.611 AC XY: 45245 AN XY: 74082

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.618

Alfa AF: 0.564 Hom.: 3065

Bravo AF: 0.612

Asia WGS AF: 0.902 AC: 3137 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.15
Dann	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs153484; hg19: chr5-150631291;