Variant 16-728516-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032304.4(HAGHL):c.410C>G(p.Ser137Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000725 in 1,379,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

HAGHL
NM_032304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.627

Variant links:

Genes affected

HAGHL (HGNC:14177): (hydroxyacylglutathione hydrolase like) Predicted to enable hydroxyacylglutathione hydrolase activity and metal ion binding activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione. [provided by Alliance of Genome Resources, Apr 2022]

HAGHL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAGHL	NM_032304.4 link	c.410C>G	p.Ser137Trp	missense_variant	5/8	ENST00000389703.8	NP_115680.1	Q6PII5-2B4DED4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAGHL	ENST00000389703.8 link	c.410C>G	p.Ser137Trp	missense_variant	5/8	1	NM_032304.4	ENSP00000374353.3		Q6PII5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000156

AC:

AN:

127998

Hom.:

AF XY:

0.0000142

AC XY:

AN XY:

70312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000422

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000725

AC:

AN:

1379036

Hom.:

Cov.:

AF XY:

0.00000735

AC XY:

AN XY:

680626

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:

0.00000929

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2024

The c.410C>G (p.S137W) alteration is located in exon 5 (coding exon 5) of the HAGHL gene. This alteration results from a C to G substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.22

T;.;T;.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.53

LIST_S2

Pathogenic

0.98

D;D;D;D;D

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.62

D;D;D;D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Benign

0.29

N;.;.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

1.2

N;N;N;N;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.0060

D;D;D;D;.

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

D;.;D;D;.

Vest4

0.58

MutPred

0.69

Loss of disorder (P = 0.0159);Loss of disorder (P = 0.0159);Loss of disorder (P = 0.0159);Loss of disorder (P = 0.0159);Loss of disorder (P = 0.0159);

MVP

0.58

MPC

0.86

ClinPred

0.36

GERP RS

-2.4

Varity_R

0.12

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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