Variant 17-67086889-G-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_014877.4(HELZ):c.5434C>G(p.Pro1812Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HELZ
NM_014877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

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 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=0.22719538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELZ	NM_014877.4 linkuse as main transcript	c.5434C>G	p.Pro1812Ala	missense_variant	32/33	ENST00000358691.10	NP_055692.3	P42694-1A0A024R8K8A0A2P0H7U5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HELZ	ENST00000358691.10 linkuse as main transcript	c.5434C>G	p.Pro1812Ala	missense_variant	32/33	1	NM_014877.4	ENSP00000351524.5	P42694-1
HELZ	ENST00000580168.5 linkuse as main transcript	c.5437C>G	p.Pro1813Ala	missense_variant	32/33	1		ENSP00000464512.1	J3QS41
HELZ	ENST00000579953.5 linkuse as main transcript	n.*2101C>G		non_coding_transcript_exon_variant	30/31	2		ENSP00000463727.1	P42694-2
HELZ	ENST00000579953.5 linkuse as main transcript	n.*2101C>G		3_prime_UTR_variant	30/31	2		ENSP00000463727.1	P42694-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249588

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727230

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000932

Hom.:

ExAC

AF:

0.00000826

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

Jun 23, 2023

The c.5434C>G (p.P1812A) alteration is located in exon 32 (coding exon 29) of the HELZ gene. This alteration results from a C to G substitution at nucleotide position 5434, causing the proline (P) at amino acid position 1812 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

0.059

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.073

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.0

N;.

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.56

T;T

Polyphen

0.15

B;.

Vest4

0.31

MutPred

0.32

Loss of glycosylation at P1812 (P = 0.0425);.;

MVP

0.53

MPC

0.16

ClinPred

0.41

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.38

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