12-50119904-C-T

Position:

• chr12-50119904-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032901.4(COX14):​c.-8-132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 693,192 control chromosomes in the GnomAD database, including 43,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10998 hom., cov: 32)
  • Exomes 𝑓: 0.34 (32163 hom.)
• Consequence: COX14 NM_032901.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490

Genes affected

COX14 (HGNC:28216): (cytochrome c oxidase assembly factor COX14) This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase (COX; also known as complex IV) subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ENSG00000272368 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-50119904-C-T is Benign according to our data. Variant chr12-50119904-C-T is described in ClinVar as [Benign]. Clinvar id is 1180260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX14	NM_032901.4	c.-8-132C>T		intron_variant		ENST00000550487.6	NP_116290.1
COX14	NM_001257133.2	c.-8-132C>T		intron_variant			NP_001244062.1
COX14	NM_001257134.2	c.-8-132C>T		intron_variant			NP_001244063.1
COX14	XM_047429769.1	c.-8-132C>T		intron_variant			XP_047285725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX14	ENST00000550487.6	c.-8-132C>T		intron_variant		1	NM_032901.4	ENSP00000446524.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56424 AN: 151772 Hom.: 10992 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.337 AC: 182497 AN: 541302 Hom.: 32163 AF XY: 0.340 AC XY: 99084 AN XY: 291176

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.372 AC: 56455 AN: 151890 Hom.: 10998 Cov.: 32 AF XY: 0.362 AC XY: 26879 AN XY: 74240

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.354

Alfa AF: 0.356 Hom.: 9649

Bravo AF: 0.375

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs7961065; hg19: chr12-50513687; COSMIC: COSV58724503;