Variant 17-67078544-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.5537C>T(p.Ser1846Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,342,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.000011 ( 0 hom. )

Consequence

HELZ
NM_014877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

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=0.061917573).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELZ	NM_014877.4 linkuse as main transcript	c.5537C>T	p.Ser1846Leu	missense_variant	33/33	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.5537C>T	p.Ser1846Leu	missense_variant	33/33	1	NM_014877.4	ENSP00000351524.5	P42694-1
HELZ	ENST00000580168.5 linkuse as main transcript	c.5540C>T	p.Ser1847Leu	missense_variant	33/33	1		ENSP00000464512.1	J3QS41
HELZ	ENST00000579953.5 linkuse as main transcript	n.*2204C>T		non_coding_transcript_exon_variant	31/31	2		ENSP00000463727.1	P42694-2
HELZ	ENST00000579953.5 linkuse as main transcript	n.*2204C>T		3_prime_UTR_variant	31/31	2		ENSP00000463727.1	P42694-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000184

AC:

AN:

162858

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

86648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000746

Gnomad SAS exome

AF:

0.0000747

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1342308

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

656642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.0000150

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.0000114

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

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

Jul 31, 2024

The c.5537C>T (p.S1846L) 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 5537, causing the serine (S) at amino acid position 1846 to be replaced by a leucine (L). 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

-0.16

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.079

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.055

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.19

Sift

Uncertain

0.021

D;.

Sift4G

Benign

0.31

T;T

Polyphen

0.031

B;.

Vest4

0.10

MutPred

0.26

Loss of relative solvent accessibility (P = 0.0414);.;

MVP

0.22

MPC

0.14

ClinPred

0.21

GERP RS

5.5

Varity_R

0.11

gMVP

0.23

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