5-151252773-C-T

Variant summary

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

The ENST00000523466.5(GM2A):c.127-6982C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 213,782 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (343 hom., cov: 26)
  • Exomes 𝑓: 0.039 (119 hom.)
• Consequence: GM2A ENST00000523466.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.528

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=-0.87).
• BP6: Variant 5-151252773-C-T is Benign according to our data. Variant chr5-151252773-C-T is described in ClinVar as [Benign]. Clinvar id is 1267493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.079 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.127-6982C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10225 AN: 149928 Hom.: 344 Cov.: 26

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0654

GnomAD4 exome AF: 0.0390 AC: 2489 AN: 63752 Hom.: 119 AF XY: 0.0402 AC XY: 1368 AN XY: 34000

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0489

Gnomad4 EAS exome AF: 0.0522

Gnomad4 SAS exome AF: 0.0571

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.0681 AC: 10220 AN: 150030 Hom.: 343 Cov.: 26 AF XY: 0.0673 AC XY: 4930 AN XY: 73200

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0495

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0642

Alfa AF: 0.0662 Hom.: 40

Asia WGS AF: 0.0820 AC: 286 AN: 3474

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 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.7
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116594022; hg19: chr5-150632334;