14-22767257-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005015.5(OXA1L):​c.73G>A​(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OXA1L
NM_005015.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
Variant links:
Genes affected
OXA1L (HGNC:8526): (OXA1L mitochondrial inner membrane protein) This gene encodes an evolutionarily conserved protein that is localized to the inner mitochondrial membrane. The encoded protein is essential for the translocation of the N-terminal tail of subunit 2 of cytochrome c oxidase, and is involved in the assembly of the cytochrome c oxidase and ATPase complexes of the mitochondrial respiratory chain. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

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=0.07200596).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OXA1LNM_005015.5 linkc.73G>A p.Val25Ile missense_variant 2/10 ENST00000612549.6 NP_005006.4 Q15070J3KNA0Q2M1J6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OXA1LENST00000612549.6 linkc.73G>A p.Val25Ile missense_variant 2/101 NM_005015.5 ENSP00000483491.2 A0A087X0L7

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000406
AC:
1
AN:
246072
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133194
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000898
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1456970
Hom.:
0
Cov.:
32
AF XY:
0.00000414
AC XY:
3
AN XY:
724896
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000287
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsAug 13, 2021The c.253G>A (p.V85I) alteration is located in exon 2 (coding exon 2) of the OXA1L gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by an isoleucine (I). 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
0.085
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
10
DANN
Benign
0.96
DEOGEN2
Benign
0.011
.;.;T;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.094
N
LIST_S2
Benign
0.63
T;.;T;T;.
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.072
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.16
N;.;.;N;N
REVEL
Benign
0.015
Sift
Benign
0.069
T;.;.;T;T
Sift4G
Uncertain
0.053
T;T;T;T;T
Polyphen
0.0040
.;.;.;B;.
Vest4
0.072
MutPred
0.28
.;.;Loss of disorder (P = 0.0996);Loss of disorder (P = 0.0996);.;
MVP
0.39
MPC
0.061
ClinPred
0.20
T
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.094

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755185718; hg19: chr14-23236466; API