chr12-50118849-T-C

Position:

• chr12-50118849-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032901.4(COX14):​c.-8-1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,026 control chromosomes in the GnomAD database, including 8,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8366 hom., cov: 32)
• Consequence: COX14 NM_032901.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.197

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-50118849-T-C is Benign according to our data. Variant chr12-50118849-T-C is described in ClinVar as [Benign]. Clinvar id is 1249856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX14	NM_032901.4	c.-8-1187T>C		intron_variant		ENST00000550487.6
COX14	NM_001257133.2	c.-9+297T>C		intron_variant
COX14	NM_001257134.2	c.-8-1187T>C		intron_variant
COX14	XM_047429769.1	c.-8-1187T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX14	ENST00000550487.6	c.-8-1187T>C		intron_variant		1	NM_032901.4	P1
	ENST00000548468.2	n.105+6548T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49716 AN: 151908 Hom.: 8371 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49711 AN: 152026 Hom.: 8366 Cov.: 32 AF XY: 0.319 AC XY: 23711 AN XY: 74330

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.321

Alfa AF: 0.343 Hom.: 2461

Bravo AF: 0.324

Asia WGS AF: 0.293 AC: 1023 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.58

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: rs7307230; hg19: chr12-50512632;