4-83416804-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133636.5(HELQ):c.3125A>G(p.Asn1042Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: HELQ NM_133636.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.35

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18397567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELQ	NM_133636.5	c.3125A>G	p.Asn1042Ser	missense_variant	17/18	ENST00000295488.8
HELQ	NM_001297755.2	c.2924A>G	p.Asn975Ser	missense_variant	16/17
HELQ	NM_001297756.2	c.1634A>G	p.Asn545Ser	missense_variant	17/18
HELQ	NM_001297757.2	c.1493A>G	p.Asn498Ser	missense_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8	c.3125A>G	p.Asn1042Ser	missense_variant	17/18	1	NM_133636.5	P1
HELQ	ENST00000510985.1	c.2924A>G	p.Asn975Ser	missense_variant	16/17	1
HELQ	ENST00000508591.5	c.*1557A>G		3_prime_UTR_variant, NMD_transcript_variant	16/17	1
HELQ	ENST00000512539.1	n.437+4759A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.3125A>G (p.N1042S) alteration is located in exon 17 (coding exon 17) of the HELQ gene. This alteration results from a A to G substitution at nucleotide position 3125, causing the asparagine (N) at amino acid position 1042 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0052	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0077
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.84	L;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.064
Sift	Benign	0.14	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0080	B;B
Vest4		0.18
MutPred		0.37		Gain of MoRF binding (P = 0.1085);.;
MVP		0.70
MPC		0.084
ClinPred		0.58	D
GERP RS		4.6
Varity_R		0.046
gMVP		0.13

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84337957;