chr1-234374112-GTT-G

Position:

• chr1-234374112-GTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001301733.1(COA6):​c.-118_-117delTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00997 in 851,492 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 0)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: COA6 NM_001301733.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0550

Genes affected

COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-234374112-GTT-G is Benign according to our data. Variant chr1-234374112-GTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1202813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0113 (7999/708590) while in subpopulation AFR AF= 0.0197 (335/17026). AF 95% confidence interval is 0.0179. There are 1 homozygotes in gnomad4_exome. There are 3985 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6	NM_001206641.3	c.213-102_213-101delTT		intron_variant		ENST00000366615.10	NP_001193570.2
COA6	NM_001301733.1	c.-118_-117delTT		5_prime_UTR_variant	1/2		NP_001288662.1
COA6	NM_001012985.2	c.123-102_123-101delTT		intron_variant			NP_001013003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366612	c.-118_-117delTT		5_prime_UTR_variant	1/2	1		ENSP00000355571.1
COA6	ENST00000366615.10	c.213-102_213-101delTT		intron_variant		1	NM_001206641.3	ENSP00000355574.5
COA6	ENST00000366613.1	c.123-102_123-101delTT		intron_variant		1		ENSP00000355572.1
COA6	ENST00000619305.1	c.-16-102_-16-101delTT		intron_variant		1		ENSP00000479686.1

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 494 AN: 142812 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00241

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.000114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000141

Gnomad OTH AF: 0.00202

GnomAD4 exome AF: 0.0113 AC: 7999 AN: 708590 Hom.: 1 AF XY: 0.0112 AC XY: 3985 AN XY: 356956

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0193

Gnomad4 EAS exome AF: 0.00660

Gnomad4 SAS exome AF: 0.00930

Gnomad4 FIN exome AF: 0.00866

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.00345 AC: 493 AN: 142902 Hom.: 4 Cov.: 0 AF XY: 0.00357 AC XY: 248 AN XY: 69436

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.00241

Gnomad4 ASJ AF: 0.000302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000230

Gnomad4 FIN AF: 0.000114

Gnomad4 NFE AF: 0.000141

Gnomad4 OTH AF: 0.00201

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

Oct 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs61077059; hg19: chr1-234509858;