Genetic Variant NM_133636.5:c.1482T>A (chr4-83443598-A-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_133636.5(HELQ):c.1482T>A(p.Ile494Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HELQ
NM_133636.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

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]

HELQ links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=1.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELQ	NM_133636.5 link	c.1482T>A	p.Ile494Ile	synonymous_variant	Exon 6 of 18	ENST00000295488.8	NP_598375.3	Q8TDG4-1
HELQ	NM_001297755.2 link	c.1281T>A	p.Ile427Ile	synonymous_variant	Exon 5 of 17		NP_001284684.2
HELQ	NM_001297756.2 link	c.-23T>A		5_prime_UTR_variant	Exon 6 of 18		NP_001284685.1
HELQ	NM_001297757.2 link	c.-69-2195T>A		intron_variant	Intron 5 of 16		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HELQ	ENST00000295488.8 link	c.1482T>A	p.Ile494Ile	synonymous_variant	Exon 6 of 18	1	NM_133636.5	ENSP00000295488.3	Q8TDG4-1
HELQ	ENST00000510985.1 link	c.1281T>A	p.Ile427Ile	synonymous_variant	Exon 5 of 17	1		ENSP00000424539.1	E3W980
HELQ	ENST00000508591.5 link	n.1466-2195T>A		intron_variant	Intron 5 of 16	1		ENSP00000424186.1	E3W982

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689962

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.7

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over