17-82436654-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000327949.15(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 ENST00000327949.15 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.674
• Publications: 22 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327949.15. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXD	NM_001330542.2	MANE Select	c.632-13G>T		intron	N/A	NP_001317471.1
	HEXD	NM_173620.3		c.632-13G>T		intron	N/A	NP_775891.2
	HEXD	NM_001369487.1		c.356-13G>T		intron	N/A	NP_001356416.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXD	ENST00000327949.15	TSL:1 MANE Select	c.632-13G>T		intron	N/A	ENSP00000332634.9
	HEXD	ENST00000337014.10	TSL:1	c.632-13G>T		intron	N/A	ENSP00000337854.6
	HEXD	ENST00000577944.5	TSL:5	c.632-13G>T		intron	N/A	ENSP00000463129.1

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

GnomAD2 exomes AF: 0.417 AC: 96254 AN: 230950 AF XY: 0.405

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 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

African (AFR) AF: 0.332 AC: 11057 AN: 33352

American (AMR) AF: 0.598 AC: 26138 AN: 43688

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9315 AN: 25940

East Asian (EAS) AF: 0.913 AC: 36068 AN: 39484

South Asian (SAS) AF: 0.407 AC: 34542 AN: 84934

European-Finnish (FIN) AF: 0.292 AC: 14356 AN: 49092

Middle Eastern (MID) AF: 0.336 AC: 1936 AN: 5758

European-Non Finnish (NFE) AF: 0.307 AC: 339392 AN: 1106444

Other (OTH) AF: 0.364 AC: 21845 AN: 59948

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

African (AFR) AF: 0.325 AC: 13517 AN: 41532

American (AMR) AF: 0.502 AC: 7674 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4689 AN: 5176

South Asian (SAS) AF: 0.411 AC: 1985 AN: 4830

European-Finnish (FIN) AF: 0.288 AC: 3056 AN: 10600

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20933 AN: 67992

Other (OTH) AF: 0.393 AC: 832 AN: 2116

Alfa AF: 0.308 Hom.: 3516

Bravo AF: 0.380

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	0.018
DANN	Benign	0.44
PhyloP100		-0.67
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4789777; hg19: chr17-80394530;