Variant 14-22769791-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_005015.5(OXA1L):c.440G>T(p.Cys147Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OXA1L
NM_005015.5 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.10

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]

OXA1L links:

OXA1L (HGNC:):

OXA1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-22769791-G-T is Pathogenic according to our data. Variant chr14-22769791-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 560160.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXA1L	NM_005015.5 linkuse as main transcript	c.440G>T	p.Cys147Phe	missense_variant, splice_region_variant	4/10	ENST00000612549.6	NP_005006.4	Q15070J3KNA0Q2M1J6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXA1L	ENST00000612549.6 linkuse as main transcript	c.440G>T	p.Cys147Phe	missense_variant, splice_region_variant	4/10	1	NM_005015.5	ENSP00000483491.2		A0A087X0L7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251416

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Mitochondrial disease

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Wellcome Centre for Mitochondrial Research, Newcastle University

Jul 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

0.00031

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

.;.;T;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;.;D;D;D;.

M_CAP

Benign

0.0096

MetaRNN

Uncertain

0.44

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.3

D;.;.;D;D;D

REVEL

Uncertain

0.29

Sift

Benign

0.035

D;.;.;D;D;D

Sift4G

Uncertain

0.043

D;D;D;D;D;D

Polyphen

1.0

.;.;.;.;D;.

Vest4

0.65

MutPred

0.47

.;.;Loss of catalytic residue at C147 (P = 0.0454);.;Loss of catalytic residue at C147 (P = 0.0454);.;

MVP

0.69

MPC

0.10

ClinPred

0.86

GERP RS

6.0

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: 0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over