14-22766759-C-A

Position:

• chr14-22766759-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005015.5(OXA1L):​c.58C>A​(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R20G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXA1L NM_005015.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29561877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXA1L	NM_005015.5	c.58C>A	p.Arg20Ser	missense_variant	1/10	ENST00000612549.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXA1L	ENST00000612549.6	c.58C>A	p.Arg20Ser	missense_variant	1/10	1	NM_005015.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.238C>A (p.R80S) alteration is located in exon 1 (coding exon 1) of the OXA1L gene. This alteration results from a C to A substitution at nucleotide position 238, causing the arginine (R) at amino acid position 80 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	.;.;T;T
Eigen	Benign	0.040
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.63	T;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N;.;.;N
REVEL	Benign	0.12
Sift	Benign	0.060	T;.;.;T
Sift4G	Benign	0.079	T;T;T;T
Polyphen		0.20	.;.;.;B
Vest4		0.32
MutPred		0.38		.;.;Loss of MoRF binding (P = 0.0414);Loss of MoRF binding (P = 0.0414);
MVP		0.72
MPC		0.098
ClinPred		0.84	D
GERP RS		5.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23235968;