14-22771096-A-T

Variant names:

• chr14-22771096-A-T
• rs193921091
• NM_005015.5:c.1018A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005015.5(OXA1L):​c.1018A>T​(p.Thr340Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T340A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXA1L NM_005015.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22125074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXA1L	NM_005015.5	c.1018A>T	p.Thr340Ser	missense_variant	Exon 8 of 10	ENST00000612549.6	NP_005006.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXA1L	ENST00000612549.6	c.1018A>T	p.Thr340Ser	missense_variant	Exon 8 of 10	1	NM_005015.5	ENSP00000483491.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.62
DEOGEN2	Benign	0.0086	.;.;T;T;.
Eigen	Benign	-0.039
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T;.;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PhyloP100		3.5
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.24	N;.;.;N;N
REVEL	Benign	0.13
Sift	Benign	0.38	T;.;.;T;T
Sift4G	Benign	0.32	T;T;T;T;T
Polyphen		0.73	.;.;.;P;.
Vest4		0.32
MutPred		0.42		.;.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP		0.47
MPC		0.077
ClinPred		0.49	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.25
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193921091; hg19: chr14-23240305;