Variant 4-83427592-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_133636.5(HELQ):c.2647A>G(p.Asn883Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,594,362 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02068001).

BP6

Variant 4-83427592-T-C is Benign according to our data. Variant chr4-83427592-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2213668.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELQ	NM_133636.5 linkuse as main transcript	c.2647A>G	p.Asn883Asp	missense_variant	13/18	ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2 linkuse as main transcript	c.2446A>G	p.Asn816Asp	missense_variant	12/17		NP_001284684.2
HELQ	NM_001297756.2 linkuse as main transcript	c.1156A>G	p.Asn386Asp	missense_variant	13/18		NP_001284685.1
HELQ	NM_001297757.2 linkuse as main transcript	c.1015A>G	p.Asn339Asp	missense_variant	12/17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2647A>G	p.Asn883Asp	missense_variant	13/18	1	NM_133636.5	ENSP00000295488	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.2446A>G	p.Asn816Asp	missense_variant	12/17	1		ENSP00000424539
HELQ	ENST00000508591.5 linkuse as main transcript	c.*1079A>G		3_prime_UTR_variant, NMD_transcript_variant	12/17	1		ENSP00000424186
HELQ	ENST00000512539.1 linkuse as main transcript	n.135A>G		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000401

AC:

AN:

232038

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

125732

show subpopulations

Gnomad AFR exome

AF:

0.0000657

Gnomad AMR exome

AF:

0.000102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000938

Gnomad NFE exome

AF:

0.000807

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000713

AC:

1028

AN:

1442018

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

493

AN XY:

717196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000937

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000941

Gnomad4 NFE exome

AF:

0.000871

Gnomad4 OTH exome

AF:

0.000874

GnomAD4 genome

AF:

0.000453

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000721

Hom.:

Bravo

AF:

0.000419

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000445

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.050

Sift

Benign

0.88

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

B;B

Vest4

0.15

MVP

0.35

MPC

0.12

ClinPred

0.016

GERP RS

-3.3

Varity_R

0.056

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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