NM_133636.5:c.916G>C

Variant names:

• chr4-83453327-C-G
• rs1494961
• NM_133636.5:c.916G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133636.5(HELQ):​c.916G>C​(p.Val306Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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]

ACMG classification

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=0.05819586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5	c.916G>C	p.Val306Leu	missense_variant	Exon 2 of 18	ENST00000295488.8	NP_598375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8	c.916G>C	p.Val306Leu	missense_variant	Exon 2 of 18	1	NM_133636.5	ENSP00000295488.3
HELQ	ENST00000510985.1	c.916G>C	p.Val306Leu	missense_variant	Exon 2 of 17	1		ENSP00000424539.1
HELQ	ENST00000508591.5	n.916G>C		non_coding_transcript_exon_variant	Exon 2 of 17	1		ENSP00000424186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.063
Sift	Benign	0.19	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0	B;B
Vest4		0.054
MutPred		0.55		Loss of methylation at K303 (P = 0.0538);Loss of methylation at K303 (P = 0.0538);
MVP		0.49
MPC		0.10
ClinPred		0.26	T
GERP RS		2.3
Varity_R		0.026
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1494961; hg19: chr4-84374480;