12-50118417-T-C

Position:

• chr12-50118417-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.-8-1619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 982,520 control chromosomes in the GnomAD database, including 39,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9008 hom., cov: 33)
  • Exomes 𝑓: 0.27 (30305 hom.)
• Consequence: COX14 NM_032901.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302

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=-0.93).
• BP6: Variant 12-50118417-T-C is Benign according to our data. Variant chr12-50118417-T-C is described in ClinVar as [Benign]. Clinvar id is 1291397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX14	NM_032901.4	c.-8-1619T>C		intron_variant		ENST00000550487.6
COX14	NM_001257133.2	c.-68-76T>C		intron_variant
COX14	NM_001257134.2	c.-8-1619T>C		intron_variant
COX14	XM_047429769.1	c.-8-1619T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX14	ENST00000550487.6	c.-8-1619T>C		intron_variant		1	NM_032901.4	P1
	ENST00000548468.2	n.105+6116T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49877 AN: 152050 Hom.: 8982 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.265 AC: 220131 AN: 830352 Hom.: 30305 AF XY: 0.265 AC XY: 101552 AN XY: 383518

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.328 AC: 49934 AN: 152168 Hom.: 9008 Cov.: 33 AF XY: 0.339 AC XY: 25196 AN XY: 74400

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.319

Alfa AF: 0.291 Hom.: 1097

Bravo AF: 0.335

Asia WGS AF: 0.512 AC: 1776 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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs56151073; hg19: chr12-50512200;