chr18-50984281-G-C

Position:

• chr18-50984281-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018696.3(ELAC1):​c.343G>C​(p.Val115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAC1 NM_018696.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.955

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]

LOC107985152 (HGNC:):

ACMG classification

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=0.111938864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC1	NM_018696.3	c.343G>C	p.Val115Leu	missense_variant	3/4	ENST00000269466.8	NP_061166.1
LOC107985152	XR_007066371.1	n.10620C>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC1	ENST00000269466.8	c.343G>C	p.Val115Leu	missense_variant	3/4	1	NM_018696.3	ENSP00000269466	P1
ELAC1	ENST00000591429.1	c.343G>C	p.Val115Leu	missense_variant	3/3	1		ENSP00000464770
ELAC1	ENST00000588577.5	c.158-206G>C		intron_variant		2		ENSP00000467389

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.343G>C (p.V115L) alteration is located in exon 3 (coding exon 2) of the ELAC1 gene. This alteration results from a G to C substitution at nucleotide position 343, causing the valine (V) at amino acid position 115 to be replaced by a leucine (L). 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	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.11	N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.28	N;.
REVEL	Benign	0.11
Sift	Benign	0.12	T;.
Sift4G	Benign	0.35	T;T
Polyphen		0.0	B;.
Vest4		0.17
MutPred		0.42		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.068
MPC		0.077
ClinPred		0.38	T
GERP RS		5.1
Varity_R		0.13
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-48510651;