Variant 14-22767279-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005015.5(OXA1L):c.95T>C(p.Leu32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,434 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OXA1L
NM_005015.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.516

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04083565).

BP6

Variant 14-22767279-T-C is Benign according to our data. Variant chr14-22767279-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2243345.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXA1L	NM_005015.5 linkuse as main transcript	c.95T>C	p.Leu32Pro	missense_variant	2/10	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.95T>C	p.Leu32Pro	missense_variant	2/10	1	NM_005015.5	ENSP00000483491.2		A0A087X0L7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

249676

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

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:

0.00000548

AC:

AN:

1460434

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.0049

.;.;T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.53

T;.;T;T;.

M_CAP

Benign

0.0023

MetaRNN

Benign

0.041

T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

0.21

N;.;.;N;N

REVEL

Benign

0.086

Sift

Benign

0.089

T;.;.;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.0

.;.;.;B;.

Vest4

0.15

MutPred

0.40

.;.;Gain of disorder (P = 0.0121);Gain of disorder (P = 0.0121);.;

MVP

0.29

MPC

0.10

ClinPred

0.055

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

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