rs763256489

Variant names:

• chr4-83426053-T-C
• rs763256489
• NM_133636.5:c.2716A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-83426053-T-C
• chr4-83426053-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133636.5(HELQ):​c.2716A>G​(p.Ile906Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 6.9e-7 (0 hom.)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.850
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12344283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133636.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	NM_133636.5	MANE Select	c.2716A>G	p.Ile906Val	missense	Exon 14 of 18	NP_598375.3	Q8TDG4-1
	HELQ	NM_001297755.2		c.2515A>G	p.Ile839Val	missense	Exon 13 of 17	NP_001284684.2	E3W980
	HELQ	NM_001297756.2		c.1225A>G	p.Ile409Val	missense	Exon 14 of 18	NP_001284685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELQ	ENST00000295488.8	TSL:1 MANE Select	c.2716A>G	p.Ile906Val	missense	Exon 14 of 18	ENSP00000295488.3	Q8TDG4-1
	HELQ	ENST00000510985.1	TSL:1	c.2515A>G	p.Ile839Val	missense	Exon 13 of 17	ENSP00000424539.1	E3W980
	HELQ	ENST00000508591.5	TSL:1	n.*1148A>G		non_coding_transcript_exon	Exon 13 of 17	ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250356 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.85e-7 AC: 1 AN: 1458792 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 725876

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109612

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.49
DEOGEN2	Benign	0.00095	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.85
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.081
Sift	Benign	0.24	T
Sift4G	Benign	0.46	T
Polyphen		0.0040	B
Vest4		0.086
MutPred		0.45		Loss of helix (P = 0.0093)
MVP		0.48
MPC		0.087
ClinPred		0.030	T
GERP RS		2.2
Varity_R		0.050
gMVP		0.14
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs763256489; hg19: chr4-84347206;