rs775585062

Variant names:

• chr5-151253220-C-A
• NM_000405.5:c.4C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151253220-C-A
• chr5-151253220-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000405.5(GM2A):​c.4C>A​(p.Gln2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q2R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GM2A NM_000405.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05068901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GM2A	NM_000405.5	c.4C>A	p.Gln2Lys	missense_variant	Exon 1 of 4	ENST00000357164.4	NP_000396.2
GM2A	NM_001167607.3	c.4C>A	p.Gln2Lys	missense_variant	Exon 1 of 4		NP_001161079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000357164.4	c.4C>A	p.Gln2Lys	missense_variant	Exon 1 of 4	1	NM_000405.5	ENSP00000349687.3
GM2A	ENST00000523466.5	c.127-6535C>A		intron_variant	Intron 2 of 3	3		ENSP00000429100.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726816

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.11
DANN	Benign	0.60
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.13
Sift	Benign	0.59	T
Sift4G	Benign	1.0	T
Polyphen		0.029	B
Vest4		0.092
MutPred		0.13		Gain of ubiquitination at Q2 (P = 0.0219);
MVP		0.23
MPC		0.085
ClinPred		0.054	T
GERP RS		-1.0
Varity_R		0.055
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150632781;