Variant rs544551424 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.95C>T(p.Pro32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,413,376 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

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=0.14363682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELAC2	NM_018127.7 linkuse as main transcript	c.95C>T	p.Pro32Leu	missense_variant	1/24	ENST00000338034.9
ELAC2	NM_173717.2 linkuse as main transcript	c.95C>T	p.Pro32Leu	missense_variant	1/24
ELAC2	NM_001165962.2 linkuse as main transcript	c.95C>T	p.Pro32Leu	missense_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.95C>T	p.Pro32Leu	missense_variant	1/24	1	NM_018127.7	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000622

AC:

AN:

160702

Hom.:

AF XY:

0.00

AC XY:

AN XY:

88642

show subpopulations

Gnomad AFR exome

AF:

0.000121

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1413376

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

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:

9.18e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.017

T;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.5

L;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.13

N;N;N;.

REVEL

Benign

0.052

Sift

Benign

0.13

T;T;T;.

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.040

B;B;.;.

Vest4

0.17

MutPred

0.26

Loss of glycosylation at P32 (P = 0.0144);Loss of glycosylation at P32 (P = 0.0144);Loss of glycosylation at P32 (P = 0.0144);Loss of glycosylation at P32 (P = 0.0144);

MVP

0.66

MPC

0.20

ClinPred

0.27

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.077

gMVP

0.44

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