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. Variant got 2 ACMG points: 2P and 0B. PM2

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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+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
COX7A1	ENST00000589154.1	c.75+32_75+35dupGGGG		intron_variant	Intron 2 of 3	5		ENSP00000468063.3
COX7A1	ENST00000437291.6	c.-67+5_-67+8dupGGGG		splice_region_variant, intron_variant	Intron 2 of 3	3		ENSP00000475885.1
COX7A1	ENST00000481297.1	n.149_152dupGGGG		non_coding_transcript_exon_variant	Exon 2 of 3	2

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

GnomAD3 exomes AF: 0.00297 AC: 557 AN: 187824 Hom.: 0 AF XY: 0.00293 AC XY: 302 AN XY: 103144

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 SAS exome AF: 0.00266

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

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00174

Gnomad4 ASJ AF: 0.00238

Gnomad4 EAS AF: 0.000644

Gnomad4 SAS AF: 0.000223

Gnomad4 FIN AF: 0.00365

Gnomad4 NFE AF: 0.00177

Gnomad4 OTH AF: 0.00203

Alfa AF: 0.00233 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3214131; hg19: chr19-36642562;