rs193921091

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-22771096-A-G
• chr14-22771096-A-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>G​(p.Thr340Ala) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXA1L NM_005015.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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=0.1931313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005015.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXA1L	NM_005015.5	MANE Select	c.1018A>G	p.Thr340Ala	missense	Exon 8 of 10	NP_005006.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXA1L	ENST00000612549.6	TSL:1 MANE Select	c.1018A>G	p.Thr340Ala	missense	Exon 8 of 10	ENSP00000483491.2
	OXA1L	ENST00000285848.9	TSL:1	c.1198A>G	p.Thr400Ala	missense	Exon 8 of 10	ENSP00000285848.5
	OXA1L	ENST00000358043.5	TSL:2	c.970A>G	p.Thr324Ala	missense	Exon 8 of 10	ENSP00000350740.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.56
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.99	T
PhyloP100		3.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.42	T
Sift4G	Benign	0.38	T
Polyphen		0.20	B
Vest4		0.34
MutPred		0.43		Gain of methylation at R339 (P = 0.0746)
MVP		0.43
MPC		0.072
ClinPred		0.35	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.29
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV53536378; COSMIC: COSV53536378;