Variant 14-22767417-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_005015.5(OXA1L):c.225+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,588,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

OXA1L
NM_005015.5 splice_region, intron

Scores

Splicing: ADA: 0.00005242

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.396

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-22767417-G-C is Benign according to our data. Variant chr14-22767417-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052047.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXA1L	NM_005015.5 linkuse as main transcript	c.225+8G>C		splice_region_variant, intron_variant		ENST00000612549.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXA1L	ENST00000612549.6 linkuse as main transcript	c.225+8G>C		splice_region_variant, intron_variant		1	NM_005015.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000713

AC:

159

AN:

223126

Hom.:

AF XY:

0.000726

AC XY:

AN XY:

121288

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00564

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000762

Gnomad FIN exome

AF:

0.0000485

Gnomad NFE exome

AF:

0.000960

Gnomad OTH exome

AF:

0.000944

GnomAD4 exome

AF:

0.000612

AC:

879

AN:

1435882

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

444

AN XY:

714046

show subpopulations

Gnomad4 AFR exome

AF:

0.000281

Gnomad4 AMR exome

AF:

0.000243

Gnomad4 ASJ exome

AF:

0.00611

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000145

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.000569

Gnomad4 OTH exome

AF:

0.000930

GnomAD4 genome

AF:

0.000486

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000612

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OXA1L-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 16, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.6

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000052

dbscSNV1_RF

Benign

0.0

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