18-50986710-A-C

Variant names:

• chr18-50986710-A-C
• NM_018696.3:c.717A>C
• ELAC1 p.Leu239Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018696.3(ELAC1):​c.717A>C​(p.Leu239Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAC1 NM_018696.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2899333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018696.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC1	NM_018696.3	MANE Select	c.717A>C	p.Leu239Phe	missense	Exon 4 of 4	NP_061166.1	Q9H777

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC1	ENST00000269466.8	TSL:1 MANE Select	c.717A>C	p.Leu239Phe	missense	Exon 4 of 4	ENSP00000269466.3	Q9H777
	ENSG00000267699	ENST00000590722.2	TSL:2	n.157+12149A>C		intron	N/A	ENSP00000465737.1	E7EUB6
	ELAC1	ENST00000858935.1		c.717A>C	p.Leu239Phe	missense	Exon 5 of 5	ENSP00000528994.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.036	D
Varity_R		0.082
gMVP		0.50
Mutation Taster		=41/59	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-48513080;