chr17-82436654-G-T

Variant names:

• chr17-82436654-G-T
• rs4789777
• NM_001330542.2:c.632-13G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330542.2(HEXD):​c.632-13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,600,844 control chromosomes in the GnomAD database, including 105,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10895 hom., cov: 34)
  • Exomes 𝑓: 0.34 (94439 hom.)
• Consequence: HEXD NM_001330542.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-82436654-G-T is Benign according to our data. Variant chr17-82436654-G-T is described in ClinVar as [Benign]. Clinvar id is 402934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEXD	NM_001330542.2	c.632-13G>T		intron_variant	Intron 6 of 12	ENST00000327949.15	NP_001317471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEXD	ENST00000327949.15	c.632-13G>T		intron_variant	Intron 6 of 12	1	NM_001330542.2	ENSP00000332634.9

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54405 AN: 152086 Hom.: 10883 Cov.: 34

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.389

GnomAD3 exomes AF: 0.417 AC: 96254 AN: 230950 Hom.: 23806 AF XY: 0.405 AC XY: 50958 AN XY: 125916

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.614

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.914

Gnomad SAS exome AF: 0.410

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.341 AC: 494649 AN: 1448640 Hom.: 94439 Cov.: 32 AF XY: 0.342 AC XY: 246115 AN XY: 720220

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.913

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.358 AC: 54444 AN: 152204 Hom.: 10895 Cov.: 34 AF XY: 0.363 AC XY: 27013 AN XY: 74418

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.393

Alfa AF: 0.300 Hom.: 2500

Bravo AF: 0.380

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.018
DANN	Benign	0.44
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;