NM_133636.5:c.2627A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_133636.5(HELQ):ā€‹c.2627A>Gā€‹(p.Tyr876Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000081 in 1,604,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000083 ( 0 hom. )

Consequence

HELQ
NM_133636.5 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HELQNM_133636.5 linkc.2627A>G p.Tyr876Cys missense_variant Exon 13 of 18 ENST00000295488.8 NP_598375.3 Q8TDG4-1
HELQNM_001297755.2 linkc.2426A>G p.Tyr809Cys missense_variant Exon 12 of 17 NP_001284684.2
HELQNM_001297756.2 linkc.1136A>G p.Tyr379Cys missense_variant Exon 13 of 18 NP_001284685.1
HELQNM_001297757.2 linkc.995A>G p.Tyr332Cys missense_variant Exon 12 of 17 NP_001284686.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HELQENST00000295488.8 linkc.2627A>G p.Tyr876Cys missense_variant Exon 13 of 18 1 NM_133636.5 ENSP00000295488.3 Q8TDG4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000828
AC:
2
AN:
241480
Hom.:
0
AF XY:
0.00000764
AC XY:
1
AN XY:
130856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000314
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000575
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:
0.00000827
AC:
12
AN:
1451810
Hom.:
0
Cov.:
29
AF XY:
0.00000969
AC XY:
7
AN XY:
722190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000467
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000180
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.23
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.057
D
MutationAssessor
Pathogenic
2.9
M;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-7.3
D;D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.016
D;D
Sift4G
Uncertain
0.017
D;D
Polyphen
1.0
D;D
Vest4
0.90
MutPred
0.52
Loss of helix (P = 0.0033);.;
MVP
0.86
MPC
0.57
ClinPred
0.99
D
GERP RS
5.6
Varity_R
0.51
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs113520876; hg19: chr4-84348765; COSMIC: COSV55024348; API