Variant chr17-67078418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014877.4(HELZ):c.5663C>T(p.Ala1888Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,598,618 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 3 hom. )

Consequence

HELZ
NM_014877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.662

Variant links:

Genes affected

HELZ (HGNC:16878): (helicase with zinc finger) HELZ is a member of the superfamily I class of RNA helicases. RNA helicases alter the conformation of RNA by unwinding double-stranded regions, thereby altering the biologic activity of the RNA molecule and regulating access to other proteins (Wagner et al., 1999 [PubMed 10471385]).[supplied by OMIM, Mar 2008]

HELZ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004594505).

BS2

High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELZ	NM_014877.4 linkuse as main transcript	c.5663C>T	p.Ala1888Val	missense_variant	33/33	ENST00000358691.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELZ	ENST00000358691.10 linkuse as main transcript	c.5663C>T	p.Ala1888Val	missense_variant	33/33	1	NM_014877.4	P3	P42694-1
HELZ	ENST00000580168.5 linkuse as main transcript	c.5666C>T	p.Ala1889Val	missense_variant	33/33	1		A1
HELZ	ENST00000579953.5 linkuse as main transcript	c.*2330C>T		3_prime_UTR_variant, NMD_transcript_variant	31/31	2			P42694-2

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000732

AC:

170

AN:

232210

Hom.:

AF XY:

0.000775

AC XY:

AN XY:

126414

show subpopulations

Gnomad AFR exome

AF:

0.000734

Gnomad AMR exome

AF:

0.000298

Gnomad ASJ exome

AF:

0.00489

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000726

Gnomad FIN exome

AF:

0.000573

Gnomad NFE exome

AF:

0.000662

Gnomad OTH exome

AF:

0.000725

GnomAD4 exome

AF:

0.000470

AC:

680

AN:

1446326

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

371

AN XY:

719044

show subpopulations

Gnomad4 AFR exome

AF:

0.000706

Gnomad4 AMR exome

AF:

0.000322

Gnomad4 ASJ exome

AF:

0.00423

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000598

Gnomad4 FIN exome

AF:

0.000754

Gnomad4 NFE exome

AF:

0.000375

Gnomad4 OTH exome

AF:

0.000519

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152292

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000793

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000725

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000975

AC:

ExAC

AF:

0.000786

AC:

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

Nov 09, 2021

The c.5663C>T (p.A1888V) alteration is located in exon 33 (coding exon 30) of the HELZ gene. This alteration results from a C to T substitution at nucleotide position 5663, causing the alanine (A) at amino acid position 1888 to be replaced by a valine (V). 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

0.070

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.9

DANN

Benign

0.82

DEOGEN2

Benign

0.073

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.82

N;.

REVEL

Benign

0.20

Sift

Benign

0.044

D;.

Sift4G

Benign

0.12

T;T

Polyphen

0.0

B;.

Vest4

0.018

MVP

0.22

MPC

0.16

ClinPred

0.0098

GERP RS

-0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.18

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

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