rs9895963

chr17-13017793-G-Achr17-13017793-G-Cchr17-13017793-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_018127.7(ELAC2):c.155C>T(p.Ser52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,607,976 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S52C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: 0.207

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005798787).
• BP6: Variant 17-13017793-G-A is Benign according to our data. Variant chr17-13017793-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00213 (324/152366) while in subpopulation AFR AF= 0.0068 (283/41588). AF 95% confidence interval is 0.00615. There are 1 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.155C>T	p.Ser52Phe	missense_variant	1/24	ENST00000338034.9
ELAC2	NM_173717.2	c.155C>T	p.Ser52Phe	missense_variant	1/24
ELAC2	NM_001165962.2	c.155C>T	p.Ser52Phe	missense_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.155C>T	p.Ser52Phe	missense_variant	1/24	1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 323 AN: 152248 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00680

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000715 AC: 160 AN: 223824 Hom.: 0 AF XY: 0.000599 AC XY: 74 AN XY: 123500

Gnomad AFR exome AF: 0.00717

Gnomad AMR exome AF: 0.000302

Gnomad ASJ exome AF: 0.00255

Gnomad EAS exome AF: 0.000469

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000366

GnomAD4 exome AF: 0.000376 AC: 548 AN: 1455610 Hom.: 3 Cov.: 31 AF XY: 0.000327 AC XY: 237 AN XY: 723740

Gnomad4 AFR exome AF: 0.00769

Gnomad4 AMR exome AF: 0.000386

Gnomad4 ASJ exome AF: 0.00243

Gnomad4 EAS exome AF: 0.000355

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.0000583

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.000766

GnomAD4 genome AF: 0.00213 AC: 324 AN: 152366 Hom.: 1 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74506

Gnomad4 AFR AF: 0.00680

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00254

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00370 AC: 16

ESP6500EA AF: 0.000352 AC: 3

ExAC AF: 0.000691 AC: 83

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 29, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 15, 2020	- -

Prostate cancer, hereditary, 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Combined oxidative phosphorylation defect type 17 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

ELAC2-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Benign	0.73
DEOGEN2	Benign	0.022	T;.;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.27	T;T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.0058	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L;.;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.2	N;N;N;.
REVEL	Benign	0.057
Sift	Benign	0.047	D;D;T;.
Sift4G	Uncertain	0.054	T;T;T;T
Polyphen		0.29	B;B;.;.
Vest4		0.085
MVP		0.75
MPC		0.20
ClinPred		0.0044	T
GERP RS		3.1
Varity_R		0.040
gMVP		0.27

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

Other links and lift over

dbSNP: rs9895963; hg19: chr17-12921110;