dbSNP rs776776755: HELQ:p.Ile842Val (chr4-83427715-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133636.5(HELQ):c.2524A>G(p.Ile842Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000362 in 1,381,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

HELQ (HGNC:18536): (helicase, POLQ like) HEL308 is a single-stranded DNA-dependent ATPase and DNA helicase (Marini and Wood, 2002 [PubMed 11751861]).[supplied by OMIM, Mar 2008]

HELQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17872462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5 link	c.2524A>G	p.Ile842Val	missense_variant	Exon 13 of 18	ENST00000295488.8	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2 link	c.2323A>G	p.Ile775Val	missense_variant	Exon 12 of 17		NP_001284684.2
HELQ	NM_001297756.2 link	c.1033A>G	p.Ile345Val	missense_variant	Exon 13 of 18		NP_001284685.1
HELQ	NM_001297757.2 link	c.892A>G	p.Ile298Val	missense_variant	Exon 12 of 17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8 link	c.2524A>G	p.Ile842Val	missense_variant	Exon 13 of 18	1	NM_133636.5	ENSP00000295488.3		Q8TDG4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000103

AC:

AN:

193522

Hom.:

AF XY:

0.00000946

AC XY:

AN XY:

105746

show subpopulations

Gnomad AFR exome

AF:

0.000150

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000362

AC:

AN:

1381226

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684626

show subpopulations

Gnomad4 AFR exome

AF:

0.000135

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:

9.32e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2524A>G (p.I842V) alteration is located in exon 13 (coding exon 13) of the HELQ gene. This alteration results from a A to G substitution at nucleotide position 2524, causing the isoleucine (I) at amino acid position 842 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

0.061

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-0.034

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.10

Sift

Benign

0.23

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.038

B;B

Vest4

0.20

MutPred

0.42

Loss of helix (P = 0.0196);.;

MVP

0.71

MPC

0.093

ClinPred

0.21

GERP RS

4.2

Varity_R

0.057

gMVP

0.17

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over