chr1-234374112-GTTTTTTT-G

Position:

• chr1-234374112-GTTTTTTT-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.-123_-117delTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 861,950 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (4 hom., cov: 0)
  • Exomes 𝑓: 0.00093 (6 hom.)
• Consequence: COA6 NM_001301733.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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-GTTTTTTT-G is Benign according to our data. Variant chr1-234374112-GTTTTTTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00606 (866/142946) while in subpopulation AFR AF= 0.0192 (773/40174). AF 95% confidence interval is 0.0181. There are 4 homozygotes in gnomad4. There are 400 alleles in male gnomad4 subpopulation. Median coverage is 0. 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.213-107_213-101delTTTTTTT		intron_variant		ENST00000366615.10	NP_001193570.2
COA6	NM_001301733.1	c.-123_-117delTTTTTTT		5_prime_UTR_variant	1/2		NP_001288662.1
COA6	NM_001012985.2	c.123-107_123-101delTTTTTTT		intron_variant			NP_001013003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366612	c.-123_-117delTTTTTTT		5_prime_UTR_variant	1/2	1		ENSP00000355571.1
COA6	ENST00000366615.10	c.213-107_213-101delTTTTTTT		intron_variant		1	NM_001206641.3	ENSP00000355574.5
COA6	ENST00000366613.1	c.123-107_123-101delTTTTTTT		intron_variant		1		ENSP00000355572.1
COA6	ENST00000619305.1	c.-16-107_-16-101delTTTTTTT		intron_variant		1		ENSP00000479686.1

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 863 AN: 142856 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00421

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.000266

Gnomad OTH AF: 0.00705

GnomAD4 exome AF: 0.000926 AC: 666 AN: 719004 Hom.: 6 AF XY: 0.000798 AC XY: 289 AN XY: 362354

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.00310

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.00241

GnomAD4 genome AF: 0.00606 AC: 866 AN: 142946 Hom.: 4 Cov.: 0 AF XY: 0.00576 AC XY: 400 AN XY: 69450

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.00420

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000266

Gnomad4 OTH AF: 0.00702

Alfa AF: 0.000148 Hom.: 457

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 02, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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;