rs2231687

Variant names:

• chr10-99713461-A-C
• rs2231687
• ENST00000370483.9:c.1120T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-99713461-A-C
• chr10-99713461-A-G
• chr10-99713461-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004376.7(COX15):​c.1120T>G​(p.Phe374Val) 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. 11/13 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. F374L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: COX15 NM_004376.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

COX15 (HGNC:2263): (cytochrome c oxidase assembly homolog COX15) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be essential for the biogenesis of COX formation and may function in the hydroxylation of heme O, according to the yeast mutant studies. This protein is predicted to contain 5 transmembrane domains localized in the mitochondrial inner membrane. Alternative splicing of this gene generates two transcript variants diverging in the 3' region. [provided by RefSeq, Jul 2008]

ENSG00000285932 (HGNC:):

CUTC (HGNC:24271): (cutC copper transporter) Members of the CUT family of copper transporters are associated with copper homeostasis and are involved in the uptake, storage, delivery, and efflux of copper (Gupta et al., 1995 [PubMed 7635807]; Li et al., 2005 [PubMed 16182249]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04944694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX15	NM_078470.6	c.*1126T>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000016171.6	NP_510870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX15	ENST00000370483.9	c.1120T>G	p.Phe374Val	missense_variant	Exon 9 of 9	1		ENSP00000359514.5
COX15	ENST00000016171	c.*1126T>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_078470.6	ENSP00000016171.6
ENSG00000285932	ENST00000649102.1	n.*460+2887T>G		intron_variant	Intron 8 of 12			ENSP00000497114.1
CUTC	ENST00000493385.5	n.117-9457A>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.5
DANN	Benign	0.87
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.022
Sift	Benign	0.80	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.51		Gain of sheet (P = 0.0477);
MVP		0.23
ClinPred		0.047	T
GERP RS		0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2231687; hg19: chr10-101473218;