rs4789777

chr17-82436654-G-Achr17-82436654-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001330542.2(HEXD):c.632-13G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,603,112 control chromosomes in the GnomAD database, including 20 homozygotes. 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 0.0024 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (19 hom.)
• Consequence: HEXD NM_001330542.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXD	NM_001330542.2	c.632-13G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000327949.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXD	ENST00000327949.15	c.632-13G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001330542.2	P1

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 359 AN: 152138 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00215 AC: 496 AN: 230950 Hom.: 2 AF XY: 0.00214 AC XY: 269 AN XY: 125916

Gnomad AFR exome AF: 0.000284

Gnomad AMR exome AF: 0.000272

Gnomad ASJ exome AF: 0.00176

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000343

Gnomad FIN exome AF: 0.00515

Gnomad NFE exome AF: 0.00346

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00175 AC: 2542 AN: 1450856 Hom.: 19 Cov.: 32 AF XY: 0.00187 AC XY: 1349 AN XY: 721256

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000457

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000588

Gnomad4 FIN exome AF: 0.00529

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00236 AC: 359 AN: 152256 Hom.: 1 Cov.: 34 AF XY: 0.00232 AC XY: 173 AN XY: 74436

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00481

Gnomad4 NFE AF: 0.00419

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00294 Hom.: 2500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.035
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4789777; hg19: chr17-80394530;