18-50984142-C-A

Variant names:

• chr18-50984142-C-A
• NM_018696.3:c.204C>A

Variant summary

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

The NM_018696.3(ELAC1):​c.204C>A​(p.Phe68Leu) 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. 14/21 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: 1.58

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]

ENSG00000267699 (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=0.14261776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC1	NM_018696.3	c.204C>A	p.Phe68Leu	missense_variant	Exon 3 of 4	ENST00000269466.8	NP_061166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC1	ENST00000269466.8	c.204C>A	p.Phe68Leu	missense_variant	Exon 3 of 4	1	NM_018696.3	ENSP00000269466.3
ENSG00000267699	ENST00000590722.2	n.157+9581C>A		intron_variant	Intron 2 of 8	2		ENSP00000465737.1

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

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.204C>A (p.F68L) alteration is located in exon 3 (coding exon 2) of the ELAC1 gene. This alteration results from a C to A substitution at nucleotide position 204, causing the phenylalanine (F) at amino acid position 68 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.47	N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.8	N;.
REVEL	Benign	0.12
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.28
MutPred		0.43		Loss of catalytic residue at F68 (P = 0.08);Loss of catalytic residue at F68 (P = 0.08);
MVP		0.12
MPC		0.091
ClinPred		0.31	T
GERP RS		3.3
Varity_R		0.34
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr18-48510512;