Variant 16-727531-G-C 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.22G>C(p.Val8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HAGHL
NM_032304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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 linkuse as main transcript	c.22G>C	p.Val8Leu	missense_variant	1/8	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.22G>C	p.Val8Leu	missense_variant	1/8	1	NM_032304.4	ENSP00000374353	P1	Q6PII5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458590

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725580

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:

9.00e-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

Mar 28, 2023

The c.22G>C (p.V8L) alteration is located in exon 1 (coding exon 1) of the HAGHL gene. This alteration results from a G to C substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a leucine (L). 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

Pathogenic

0.69

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

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

Eigen

Benign

0.11

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.92

.;D;.;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.47

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

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.3

L;L;.;L;.;.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

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

REVEL

Uncertain

0.61

Sift

Uncertain

0.027

D;D;.;D;T;T;D;T;.;D

Sift4G

Benign

0.21

T;T;.;T;T;T;D;T;T;T

Polyphen

0.94

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

Vest4

0.42

MutPred

0.61

Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);Gain of catalytic residue at V8 (P = 0.0401);

MVP

0.77

MPC

0.60

ClinPred

0.88

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over