chr5-151253173-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000523466.5(GM2A):​c.127-6582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,440,642 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

GM2A
ENST00000523466.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0220
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 5-151253173-G-A is Benign according to our data. Variant chr5-151253173-G-A is described in ClinVar as [Benign]. Clinvar id is 352250.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1604/152264) while in subpopulation AFR AF= 0.0362 (1502/41542). AF 95% confidence interval is 0.0346. There are 27 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GM2ANM_000405.5 linkuse as main transcript upstream_gene_variant ENST00000357164.4
GM2ANM_001167607.3 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GM2AENST00000523466.5 linkuse as main transcriptc.127-6582G>A intron_variant 3
GM2AENST00000357164.4 linkuse as main transcript upstream_gene_variant 1 NM_000405.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0105
AC:
1605
AN:
152146
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0363
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00282
AC:
707
AN:
251130
Hom.:
14
AF XY:
0.00210
AC XY:
285
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.0390
Gnomad AMR exome
AF:
0.00162
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00107
AC:
1382
AN:
1288378
Hom.:
24
Cov.:
19
AF XY:
0.000914
AC XY:
594
AN XY:
649974
show subpopulations
Gnomad4 AFR exome
AF:
0.0358
Gnomad4 AMR exome
AF:
0.00175
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000241
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000545
Gnomad4 OTH exome
AF:
0.00298
GnomAD4 genome
AF:
0.0105
AC:
1604
AN:
152264
Hom.:
27
Cov.:
32
AF XY:
0.0102
AC XY:
757
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0362
Gnomad4 AMR
AF:
0.00458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00169
Hom.:
1
Bravo
AF:
0.0119
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Tay-Sachs disease, variant AB Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.5
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144932594; hg19: chr5-150632734; API