Variant 4-83429581-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133636.5(HELQ):c.2461G>A(p.Glu821Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.863

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057374597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELQ	NM_133636.5 linkuse as main transcript	c.2461G>A	p.Glu821Lys	missense_variant	12/18	ENST00000295488.8	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2 linkuse as main transcript	c.2260G>A	p.Glu754Lys	missense_variant	11/17		NP_001284684.2
HELQ	NM_001297756.2 linkuse as main transcript	c.970G>A	p.Glu324Lys	missense_variant	12/18		NP_001284685.1
HELQ	NM_001297757.2 linkuse as main transcript	c.829G>A	p.Glu277Lys	missense_variant	11/17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2461G>A	p.Glu821Lys	missense_variant	12/18	1	NM_133636.5	ENSP00000295488.3	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.2260G>A	p.Glu754Lys	missense_variant	11/17	1		ENSP00000424539.1	E3W980
HELQ	ENST00000508591.5 linkuse as main transcript	n.*893G>A		non_coding_transcript_exon_variant	11/17	1		ENSP00000424186.1	E3W982
HELQ	ENST00000508591.5 linkuse as main transcript	n.*893G>A		3_prime_UTR_variant	11/17	1		ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251066

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.0000103

AC:

AN:

1460384

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2024

The c.2461G>A (p.E821K) alteration is located in exon 12 (coding exon 12) of the HELQ gene. This alteration results from a G to A substitution at nucleotide position 2461, causing the glutamic acid (E) at amino acid position 821 to be replaced by a lysine (K). 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

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0049

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.061

Sift

Benign

0.56

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.46

Gain of ubiquitination at E821 (P = 0.0128);.;

MVP

0.44

MPC

0.12

ClinPred

0.043

GERP RS

1.5

Varity_R

0.045

gMVP

0.26

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