NM_001330542.2:c.632-13G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001330542.2(HEXD):​c.632-13G>A variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAdExome4 at 19 AR gene

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.632-13G>A		intron	N/A	NP_001317471.1	Q8WVB3-1
	HEXD	NM_173620.3		c.632-13G>A		intron	N/A	NP_775891.2	Q8WVB3-2
	HEXD	NM_001369487.1		c.356-13G>A		intron	N/A	NP_001356416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXD	ENST00000327949.15	TSL:1 MANE Select	c.632-13G>A		intron	N/A	ENSP00000332634.9	Q8WVB3-1
	HEXD	ENST00000337014.10	TSL:1	c.632-13G>A		intron	N/A	ENSP00000337854.6	Q8WVB3-2
	HEXD	ENST00000577944.5	TSL:5	c.632-13G>A		intron	N/A	ENSP00000463129.1	J3QKL0

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

GnomAD2 exomes AF: 0.00215 AC: 496 AN: 230950 AF XY: 0.00214

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 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

African (AFR) AF: 0.000120 AC: 4 AN: 33394

American (AMR) AF: 0.000457 AC: 20 AN: 43724

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 36 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.0000588 AC: 5 AN: 85012

European-Finnish (FIN) AF: 0.00529 AC: 260 AN: 49178

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.00191 AC: 2115 AN: 1108300

Other (OTH) AF: 0.00165 AC: 99 AN: 60042

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

African (AFR) AF: 0.000120 AC: 5 AN: 41550

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00481 AC: 51 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00419 AC: 285 AN: 68010

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00211 Hom.: 3516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.035
DANN	Benign	0.55
PhyloP100		-0.67
PromoterAI		-0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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;