chr19-36151660-A-ACCCCC

Variant names:

• chr19-36151660-A-ACCCCC
• rs3214131
• NM_001864.4:c.102+4_102+8dupGGGGG

Variant summary

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

The NM_001864.4(COX7A1):​c.102+4_102+8dupGGGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000451 in 144,068 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 0.00045 (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+4_102+8dupGGGGG		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+4_102+8dupGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3

Frequencies

GnomAD3 genomes AF: 0.000458 AC: 66 AN: 143958 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000383

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.000624

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000858

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000443

Gnomad OTH AF: 0.00154

GnomAD2 exomes AF: 0.0108 AC: 2030 AN: 187824 AF XY: 0.0108

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.0272

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.00351

Gnomad FIN exome AF: 0.00815

Gnomad NFE exome AF: 0.00798

Gnomad OTH exome AF: 0.00966

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.000451 AC: 65 AN: 144068 Hom.: 0 Cov.: 32 AF XY: 0.000500 AC XY: 35 AN XY: 69984

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

African (AFR) AF: 0.000382 AC: 15 AN: 39260

American (AMR) AF: 0.000554 AC: 8 AN: 14438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3362

East Asian (EAS) AF: 0.000215 AC: 1 AN: 4642

South Asian (SAS) AF: 0.00 AC: 0 AN: 4470

European-Finnish (FIN) AF: 0.000858 AC: 8 AN: 9324

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

European-Non Finnish (NFE) AF: 0.000443 AC: 29 AN: 65454

Other (OTH) AF: 0.00152 AC: 3 AN: 1972

⚠️ 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: 0.00739 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;