Variant 4-83429623-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133636.5(HELQ):c.2419A>G(p.Thr807Ala) 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. 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HELQ
NM_133636.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 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=0.111492634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HELQ	NM_133636.5 linkuse as main transcript	c.2419A>G	p.Thr807Ala	missense_variant	12/18	ENST00000295488.8	NP_598375.3
HELQ	NM_001297755.2 linkuse as main transcript	c.2218A>G	p.Thr740Ala	missense_variant	11/17		NP_001284684.2
HELQ	NM_001297756.2 linkuse as main transcript	c.928A>G	p.Thr310Ala	missense_variant	12/18		NP_001284685.1
HELQ	NM_001297757.2 linkuse as main transcript	c.787A>G	p.Thr263Ala	missense_variant	11/17		NP_001284686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2419A>G	p.Thr807Ala	missense_variant	12/18	1	NM_133636.5	ENSP00000295488	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.2218A>G	p.Thr740Ala	missense_variant	11/17	1		ENSP00000424539
HELQ	ENST00000508591.5 linkuse as main transcript	c.*851A>G		3_prime_UTR_variant, NMD_transcript_variant	11/17	1		ENSP00000424186

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726634

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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.2419A>G (p.T807A) alteration is located in exon 12 (coding exon 12) of the HELQ gene. This alteration results from a A to G substitution at nucleotide position 2419, causing the threonine (T) at amino acid position 807 to be replaced by an alanine (A). 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

0.092

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.055

Sift

Benign

0.52

T;T

Sift4G

Benign

0.91

T;T

Polyphen

0.0070

B;B

Vest4

0.13

MutPred

0.35

Loss of phosphorylation at T807 (P = 0.0474);.;

MVP

0.50

MPC

0.10

ClinPred

0.36

GERP RS

4.2

Varity_R

0.14

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over