chr5-151252773-C-T

Variant names:

• chr5-151252773-C-T
• rs116594022
• ENST00000523466.5:c.127-6982C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000523466.5	c.127-6982C>T		intron_variant	Intron 2 of 3	3		ENSP00000429100.1

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

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;