4-83421714-T-C

Variant names:

• chr4-83421714-T-C
• rs200137034
• NM_133636.5:c.2798A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_133636.5(HELQ):​c.2798A>G​(p.Asn933Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10666582).

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.2798A>G	p.Asn933Ser	missense	Exon 15 of 18	NP_598375.3	Q8TDG4-1
	HELQ	NM_001297755.2		c.2597A>G	p.Asn866Ser	missense	Exon 14 of 17	NP_001284684.2	E3W980
	HELQ	NM_001297756.2		c.1307A>G	p.Asn436Ser	missense	Exon 15 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.2798A>G	p.Asn933Ser	missense	Exon 15 of 18	ENSP00000295488.3	Q8TDG4-1
	HELQ	ENST00000510985.1	TSL:1	c.2597A>G	p.Asn866Ser	missense	Exon 14 of 17	ENSP00000424539.1	E3W980
	HELQ	ENST00000508591.5	TSL:1	n.*1230A>G		non_coding_transcript_exon	Exon 14 of 17	ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 249788 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460970 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726782

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.000202 AC: 9 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111668

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152360 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000818 Hom.: 0

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.5
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.29
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Polyphen		0.13	B
Vest4		0.34
MVP		0.72
MPC		0.093
ClinPred		0.10	T
GERP RS		3.9
Varity_R		0.15
gMVP		0.23
Mutation Taster		=91/9	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: rs200137034; hg19: chr4-84342867;