Variant chr16-728325-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032304.4(HAGHL):c.298A>G(p.Ile100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HAGHL
NM_032304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2978227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAGHL	NM_032304.4 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant	4/8	ENST00000389703.8	NP_115680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAGHL	ENST00000389703.8 linkuse as main transcript	c.298A>G	p.Ile100Val	missense_variant	4/8	1	NM_032304.4	ENSP00000374353	P1	Q6PII5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1405270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695644

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

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:

9.19e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 13, 2023

The c.298A>G (p.I100V) alteration is located in exon 4 (coding exon 4) of the HAGHL gene. This alteration results from a A to G substitution at nucleotide position 298, causing the isoleucine (I) at amino acid position 100 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.85

DEOGEN2

Benign

0.23

.;T;.;.;T;.;T;.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.82

.;T;T;T;T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.68

N;N;N;.;.;N;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.94

N;N;N;N;N;N;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.28

T;T;T;T;T;T;.;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T;T

Polyphen

0.92

P;P;P;.;D;D;.;.;.

Vest4

0.35

MutPred

0.51

Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);Gain of methylation at R103 (P = 0.0955);.;

MVP

0.49

MPC

0.39

ClinPred

0.79

GERP RS

3.2

Varity_R

0.15

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Other links and lift over