Variant 4-83432241-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_133636.5(HELQ):c.2075C>G(p.Ala692Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,427,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

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=0.069040686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HELQ	NM_133636.5 linkuse as main transcript	c.2075C>G	p.Ala692Gly	missense_variant	10/18	ENST00000295488.8
HELQ	NM_001297755.2 linkuse as main transcript	c.1874C>G	p.Ala625Gly	missense_variant	9/17
HELQ	NM_001297756.2 linkuse as main transcript	c.584C>G	p.Ala195Gly	missense_variant	10/18
HELQ	NM_001297757.2 linkuse as main transcript	c.443C>G	p.Ala148Gly	missense_variant	9/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2075C>G	p.Ala692Gly	missense_variant	10/18	1	NM_133636.5	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.1874C>G	p.Ala625Gly	missense_variant	9/17	1
HELQ	ENST00000508591.5 linkuse as main transcript	c.*507C>G		3_prime_UTR_variant, NMD_transcript_variant	9/17	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000295

AC:

AN:

237242

Hom.:

AF XY:

0.0000465

AC XY:

AN XY:

128940

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:

0.000245

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1427338

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

709708

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:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

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 05, 2024

The c.2075C>G (p.A692G) alteration is located in exon 10 (coding exon 10) of the HELQ gene. This alteration results from a C to G substitution at nucleotide position 2075, causing the alanine (A) at amino acid position 692 to be replaced by a glycine (G). 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

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.86

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0093

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.1

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.90

N;N

REVEL

Benign

0.11

Sift

Benign

0.85

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

B;B

Vest4

0.26

MutPred

0.52

Gain of methylation at K697 (P = 0.1125);.;

MVP

0.41

MPC

0.11

ClinPred

0.12

GERP RS

5.2

Varity_R

0.22

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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