17-13015806-C-T

Position:

chr17-13015806-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018127.7(ELAC2):c.394G>A(p.Gly132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000129 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.17

Variant links:

Genes affected

ELAC2 (HGNC:14198): (elaC ribonuclease Z 2) The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3' trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ELAC2 links:

ELAC2 (HGNC:):

ELAC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7 linkuse as main transcript	c.394G>A	p.Gly132Arg	missense_variant	4/24	ENST00000338034.9	NP_060597.4	Q9BQ52-1A0A0S2Z5M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.394G>A	p.Gly132Arg	missense_variant	4/24	1	NM_018127.7	ENSP00000337445.4		Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251170

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1461724

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

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:

0.000168

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 17

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Phosphorus, Inc.	Aug 01, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 25, 2022	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 132 of the ELAC2 protein (p.Gly132Arg). This variant is present in population databases (rs374005835, gnomAD 0.009%). This missense change has been observed in individual(s) with complex hyperkinetic syndrome and acanthocytosis (PMID: 30217939). ClinVar contains an entry for this variant (Variation ID: 488161). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;.;T;T;T;T;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.79

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.12

MutationAssessor

Pathogenic

3.1

M;.;M;.;.;.;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-7.3

D;D;D;.;.;.;.;.;.

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D;.;.;.;.;.;.

Sift4G

Uncertain

0.0040

D;D;D;.;D;.;.;.;D

Polyphen

1.0

D;D;.;.;.;.;.;.;.

Vest4

0.83

MutPred

0.50

Gain of solvent accessibility (P = 0.0037);.;Gain of solvent accessibility (P = 0.0037);.;.;.;.;.;Gain of solvent accessibility (P = 0.0037);

MVP

0.95

MPC

0.82

ClinPred

0.93

GERP RS

4.7

Varity_R

0.85

gMVP

0.83

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