chr19-36151660-A-ACC

Variant names:

• chr19-36151660-A-ACC
• rs3214131
• NM_001864.4:c.102+7_102+8dupGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001864.4(COX7A1):​c.102+7_102+8dupGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 1,061,634 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX7A1	NM_001864.4	c.102+7_102+8dupGG		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+7_102+8dupGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000471 AC: 5 AN: 1061634 Hom.: 0 Cov.: 31 AF XY: 0.00000562 AC XY: 3 AN XY: 533716

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

African (AFR) AF: 0.00 AC: 0 AN: 26298

American (AMR) AF: 0.00 AC: 0 AN: 33734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20064

East Asian (EAS) AF: 0.0000361 AC: 1 AN: 27714

South Asian (SAS) AF: 0.00 AC: 0 AN: 74436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4346

European-Non Finnish (NFE) AF: 0.00000381 AC: 3 AN: 788310

Other (OTH) AF: 0.0000227 AC: 1 AN: 44042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000852), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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;