Variant 18-50984377-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018696.3(ELAC1):c.439C>G(p.Pro147Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ELAC1
NM_018696.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.452

Variant links:

Genes affected

ELAC1 (HGNC:14197): (elaC ribonuclease Z 1) Predicted to enable 3'-tRNA processing endoribonuclease activity. Predicted to be involved in tRNA 3'-trailer cleavage, endonucleolytic. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ELAC1 links:

LOC107985152 (HGNC:):

LOC107985152 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04795468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC1	NM_018696.3 linkuse as main transcript	c.439C>G	p.Pro147Ala	missense_variant	3/4	ENST00000269466.8	NP_061166.1
LOC107985152	XR_007066371.1 linkuse as main transcript	n.10561-37G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ELAC1	ENST00000269466.8 linkuse as main transcript	c.439C>G	p.Pro147Ala	missense_variant	3/4	1	NM_018696.3	ENSP00000269466	P1
ELAC1	ENST00000591429.1 linkuse as main transcript	c.439C>G	p.Pro147Ala	missense_variant	3/3	1		ENSP00000464770
ELAC1	ENST00000588577.5 linkuse as main transcript	c.158-110C>G		intron_variant		2		ENSP00000467389

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251278

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135822

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727232

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:

0.0000674

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

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

May 07, 2024

The c.439C>G (p.P147A) alteration is located in exon 3 (coding exon 2) of the ELAC1 gene. This alteration results from a C to G substitution at nucleotide position 439, causing the proline (P) at amino acid position 147 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

0.058

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.029

DANN

Benign

0.73

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.59

N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.66

N;.

REVEL

Benign

0.078

Sift

Benign

0.63

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.0090

B;.

Vest4

0.23

MutPred

0.30

Loss of catalytic residue at P147 (P = 0.0196);Loss of catalytic residue at P147 (P = 0.0196);

MVP

0.068

MPC

0.077

ClinPred

0.049

GERP RS

0.15

Varity_R

0.032

gMVP

0.19

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