18-50986710-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018696.3(ELAC1):c.717A>T(p.Leu239Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
ELAC1
NM_018696.3 missense
NM_018696.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 1.60
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]
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ACMG classification
Classification made for transcript
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=0.09127918).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELAC1 | NM_018696.3 | c.717A>T | p.Leu239Phe | missense_variant | 4/4 | ENST00000269466.8 | NP_061166.1 | |
LOC107985152 | XR_007066371.1 | n.10560+1929T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELAC1 | ENST00000269466.8 | c.717A>T | p.Leu239Phe | missense_variant | 4/4 | 1 | NM_018696.3 | ENSP00000269466 | P1 | |
ELAC1 | ENST00000588577.5 | c.*59A>T | 3_prime_UTR_variant | 4/4 | 2 | ENSP00000467389 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251350Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135842
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727236
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74462
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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 | Dec 04, 2023 | The c.717A>T (p.L239F) alteration is located in exon 4 (coding exon 3) of the ELAC1 gene. This alteration results from a A to T substitution at nucleotide position 717, causing the leucine (L) at amino acid position 239 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of methylation at K240 (P = 0.0303);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at