chr19-35654507-CA-C

Position:

• chr19-35654507-CA-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001863.5(COX6B1):​c.107-49delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (1 hom., cov: 31)
  • Exomes 𝑓: 0.34 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: COX6B1 NM_001863.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.573

Genes affected

COX6B1 (HGNC:2280): (cytochrome c oxidase subunit 6B1) Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Mutations in this gene are associated with severe infantile encephalomyopathy. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 19-35654507-CA-C is Benign according to our data. Variant chr19-35654507-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187385.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX6B1	NM_001863.5	c.107-49delA		intron_variant		ENST00000649813.2	NP_001854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX6B1	ENST00000649813.2	c.107-49delA		intron_variant			NM_001863.5	ENSP00000497926.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1101 AN: 134592 Hom.: 1 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00729

Gnomad ASJ AF: 0.00310

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.00326

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.00709

Gnomad NFE AF: 0.00596

Gnomad OTH AF: 0.00451

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.337 AC: 355005 AN: 1053848 Hom.: 2 AF XY: 0.343 AC XY: 181691 AN XY: 529824

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00829 AC: 1116 AN: 134632 Hom.: 1 Cov.: 31 AF XY: 0.00898 AC XY: 584 AN XY: 65008

Gnomad4 AFR AF: 0.00736

Gnomad4 AMR AF: 0.00743

Gnomad4 ASJ AF: 0.00310

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.00350

Gnomad4 FIN AF: 0.0366

Gnomad4 NFE AF: 0.00596

Gnomad4 OTH AF: 0.00504

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs377609041; hg19: chr19-36145409;