19-36151660-AC-ACCCCCCCCCCCCC

Variant names:

• chr19-36151660-A-ACCCCCCCCCCCC
• rs3214131
• NM_001864.4:c.102+8_102+9insGGGGGGGGGGGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001864.4(COX7A1):​c.102+8_102+9insGGGGGGGGGGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 144,222 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000014 (0 hom., cov: 32)
• Consequence: COX7A1 NM_001864.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 0 publications found

Genes affected

COX7A1 (HGNC:2287): (cytochrome c oxidase subunit 7A1) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component 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 function in the regulation and assembly of the complex. This nuclear gene encodes polypeptide 1 (muscle isoform) of subunit VIIa and the polypeptide 1 is present only in muscle tissues. Other polypeptides of subunit VIIa are present in both muscle and nonmuscle tissues, and are encoded by different genes. [provided by RefSeq, Jul 2008]

ENSG00000294115 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX7A1	NM_001864.4	c.102+8_102+9insGGGGGGGGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000292907.8	NP_001855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX7A1	ENST00000292907.8	c.102+8_102+9insGGGGGGGGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 144104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 144222 Hom.: 0 Cov.: 32 AF XY: 0.0000143 AC XY: 1 AN XY: 70076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000255 AC: 1 AN: 39290

American (AMR) AF: 0.00 AC: 0 AN: 14446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.00 AC: 0 AN: 4660

South Asian (SAS) AF: 0.00 AC: 0 AN: 4482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65514

Other (OTH) AF: 0.00 AC: 0 AN: 1976

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.072

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3214131; hg19: chr19-36642562;