rs62022857

Positions:

• chr15-72345284-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000520.6(HEXA):​c.1526+162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HEXA NM_000520.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

HEXA (HGNC:4878): (hexosaminidase subunit alpha) This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEXA	NM_000520.6	c.1526+162G>A		intron_variant		ENST00000268097.10	NP_000511.2
HEXA	NM_001318825.2	c.1559+162G>A		intron_variant			NP_001305754.1
HEXA	NR_134869.3	n.1473G>A		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEXA	ENST00000268097.10	c.1526+162G>A		intron_variant		1	NM_000520.6	ENSP00000268097	P1
	ENST00000570175.1	n.166-102C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 150212 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.0000999

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 169 AN: 1209562 Hom.: 0 Cov.: 17 AF XY: 0.000155 AC XY: 92 AN XY: 595168

Gnomad4 AFR exome AF: 0.000113

Gnomad4 AMR exome AF: 0.000247

Gnomad4 ASJ exome AF: 0.0000922

Gnomad4 EAS exome AF: 0.000122

Gnomad4 SAS exome AF: 0.000654

Gnomad4 FIN exome AF: 0.0000622

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.000198

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000133 AC: 2 AN: 150212 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73138

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.0000999

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs62022857; hg19: chr15-72637625;