17-82419814-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001330542.2(HEXD):​c.15T>C​(p.Thr5Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T5T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HEXD NM_001330542.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.

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>C	p.Thr5Thr	synonymous	Exon 2 of 13	NP_001317471.1	Q8WVB3-1
	HEXD	NM_173620.3		c.15T>C	p.Thr5Thr	synonymous	Exon 2 of 12	NP_775891.2	Q8WVB3-2
	HEXD	NM_001369487.1		c.-360T>C		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>C	p.Thr5Thr	synonymous	Exon 2 of 13	ENSP00000332634.9	Q8WVB3-1
	HEXD	ENST00000337014.10	TSL:1	c.15T>C	p.Thr5Thr	synonymous	Exon 2 of 12	ENSP00000337854.6	Q8WVB3-2
	HEXD	ENST00000577944.5	TSL:5	c.15T>C	p.Thr5Thr	synonymous	Exon 2 of 13	ENSP00000463129.1	J3QKL0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455724 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724570

African (AFR) AF: 0.00 AC: 0 AN: 33244

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106784

Other (OTH) AF: 0.00 AC: 0 AN: 60178

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.63
PhyloP100		-2.2
PromoterAI		-0.017	Neutral

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;