chr19-36151660-A-ACCCCCCCCCCC

Variant names:

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

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+9insGGGGGGGGGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 144,206 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 0.0000069 (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+9insGGGGGGGGGGG		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+9insGGGGGGGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3

Frequencies

GnomAD3 genomes AF: 0.00000694 AC: 1 AN: 144090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000693

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000693 AC: 1 AN: 144206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 70070

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

African (AFR) AF: 0.00 AC: 0 AN: 39290

American (AMR) AF: 0.0000692 AC: 1 AN: 14444

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 4478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9340

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65512

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;