Variant 17-13017850-C-T 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_018127.7(ELAC2):c.98G>A(p.Arg33His) variant causes a missense change. The variant allele was found at a frequency of 0.00000283 in 1,412,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000028 ( 0 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26

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:

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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=0.118240535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ELAC2	NM_018127.7 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	1/24	ENST00000338034.9	NP_060597.4
ELAC2	NM_173717.2 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	1/24		NP_776065.1
ELAC2	NM_001165962.2 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	1/23		NP_001159434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	1/24	1	NM_018127.7	ENSP00000337445	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000627

AC:

AN:

159580

Hom.:

AF XY:

0.00

AC XY:

AN XY:

88084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000381

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1412312

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000264

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:

0.00000184

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000934

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.49

T;T;T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.11

N;N;N;.

REVEL

Benign

0.080

Sift

Benign

0.20

T;T;T;.

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.12

MutPred

0.26

Loss of glycosylation at P32 (P = 0.0513);Loss of glycosylation at P32 (P = 0.0513);Loss of glycosylation at P32 (P = 0.0513);Loss of glycosylation at P32 (P = 0.0513);

MVP

0.74

MPC

0.23

ClinPred

0.37

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.056

gMVP

0.30

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over