17-82419814-T-G

Variant names:

• chr17-82419814-T-G
• rs1141463
• NM_001330542.2:c.15T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001330542.2(HEXD):​c.15T>G​(p.Thr5Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,601,768 control chromosomes in the GnomAD database, including 94,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14706 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79455 hom.)
• Consequence: HEXD NM_001330542.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.20
• Publications: 33 publications found

Genes affected

HEXD (HGNC:26307): (hexosaminidase D) Enables beta-N-acetylhexosaminidase activity. Predicted to be involved in carbohydrate metabolic process. Located in extracellular vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-82419814-T-G is Benign according to our data. Variant chr17-82419814-T-G is described in ClinVar as Benign. ClinVar VariationId is 402932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330542.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXD	NM_001330542.2	MANE Select	c.15T>G	p.Thr5Thr	synonymous	Exon 2 of 13	NP_001317471.1	Q8WVB3-1
	HEXD	NM_173620.3		c.15T>G	p.Thr5Thr	synonymous	Exon 2 of 12	NP_775891.2	Q8WVB3-2
	HEXD	NM_001369487.1		c.-360T>G		5_prime_UTR	Exon 2 of 15	NP_001356416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXD	ENST00000327949.15	TSL:1 MANE Select	c.15T>G	p.Thr5Thr	synonymous	Exon 2 of 13	ENSP00000332634.9	Q8WVB3-1
	HEXD	ENST00000337014.10	TSL:1	c.15T>G	p.Thr5Thr	synonymous	Exon 2 of 12	ENSP00000337854.6	Q8WVB3-2
	HEXD	ENST00000577944.5	TSL:5	c.15T>G	p.Thr5Thr	synonymous	Exon 2 of 13	ENSP00000463129.1	J3QKL0

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62173 AN: 151956 Hom.: 14663 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.356 AC: 88312 AN: 248414 AF XY: 0.341

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.700

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.317 AC: 460111 AN: 1449692 Hom.: 79455 Cov.: 29 AF XY: 0.314 AC XY: 226351 AN XY: 721826

African (AFR) AF: 0.632 AC: 20933 AN: 33108

American (AMR) AF: 0.415 AC: 18447 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7776 AN: 26032

East Asian (EAS) AF: 0.713 AC: 28210 AN: 39548

South Asian (SAS) AF: 0.267 AC: 22970 AN: 85906

European-Finnish (FIN) AF: 0.254 AC: 13527 AN: 53330

Middle Eastern (MID) AF: 0.262 AC: 1505 AN: 5742

European-Non Finnish (NFE) AF: 0.296 AC: 326339 AN: 1101584

Other (OTH) AF: 0.340 AC: 20404 AN: 59944

GnomAD4 genome AF: 0.409 AC: 62265 AN: 152076 Hom.: 14706 Cov.: 32 AF XY: 0.404 AC XY: 30063 AN XY: 74348

African (AFR) AF: 0.623 AC: 25826 AN: 41472

American (AMR) AF: 0.395 AC: 6038 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.708 AC: 3667 AN: 5176

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4812

European-Finnish (FIN) AF: 0.247 AC: 2616 AN: 10580

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20410 AN: 67970

Other (OTH) AF: 0.415 AC: 878 AN: 2116

Alfa AF: 0.324 Hom.: 10829

Bravo AF: 0.434

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.099
DANN	Benign	0.63
PhyloP100		-2.2
PromoterAI		0.078	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1141463; hg19: chr17-80377690; COSMIC: COSV57341028; COSMIC: COSV57341028;