Variant 17-82433808-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001330542.2(HEXD):c.433A>T(p.Ile145Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,459,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I145V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

HEXD
NM_001330542.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

Variant links:

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]

HEXD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEXD	NM_001330542.2 linkuse as main transcript	c.433A>T	p.Ile145Phe	missense_variant	5/13	ENST00000327949.15	NP_001317471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEXD	ENST00000327949.15 linkuse as main transcript	c.433A>T	p.Ile145Phe	missense_variant	5/13	1	NM_001330542.2	ENSP00000332634	P1	Q8WVB3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1459856

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Benign

0.38

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.93

D;.;D;D;T

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.95

D;D;D;D;D

MetaSVM

Pathogenic

0.84

MutationTaster

Benign

0.45

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.9

D;D;.;.;.

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

D;D;.;.;.

Sift4G

Uncertain

0.0020

D;D;D;D;.

Vest4

0.46

MutPred

0.77

Gain of methylation at R142 (P = 0.1433);Gain of methylation at R142 (P = 0.1433);.;Gain of methylation at R142 (P = 0.1433);Gain of methylation at R142 (P = 0.1433);

MVP

0.64

MPC

0.92

ClinPred

0.98

GERP RS

0.036

gMVP

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over