19-36151660-AC-ACCCCC

Variant names:

• chr19-36151660-A-ACCCC
• rs3214131
• NM_001864.4:c.102+5_102+8dupGGGG

Variant summary

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

The NM_001864.4(COX7A1):​c.102+5_102+8dupGGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 144,030 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0020 (0 hom., cov: 32)
• Consequence: COX7A1 NM_001864.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 3 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+5_102+8dupGGGG		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+5_102+8dupGGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 291 AN: 143914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00174

Gnomad ASJ AF: 0.00238

Gnomad EAS AF: 0.000642

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.00365

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.00205

GnomAD2 exomes AF: 0.00297 AC: 557 AN: 187824 AF XY: 0.00293

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00667

Gnomad ASJ exome AF: 0.00446

Gnomad EAS exome AF: 0.00358

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.00349

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00202 AC: 291 AN: 144030 Hom.: 0 Cov.: 32 AF XY: 0.00190 AC XY: 133 AN XY: 69966

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

African (AFR) AF: 0.00255 AC: 100 AN: 39226

American (AMR) AF: 0.00174 AC: 25 AN: 14398

Ashkenazi Jewish (ASJ) AF: 0.00238 AC: 8 AN: 3362

East Asian (EAS) AF: 0.000644 AC: 3 AN: 4656

South Asian (SAS) AF: 0.000223 AC: 1 AN: 4480

European-Finnish (FIN) AF: 0.00365 AC: 34 AN: 9322

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

European-Non Finnish (NFE) AF: 0.00177 AC: 116 AN: 65464

Other (OTH) AF: 0.00203 AC: 4 AN: 1974

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00233 Hom.: 0

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;