chr19-36151660-A-ACCCCCC

Variant names:

• chr19-36151660-A-ACCCCCC
• rs3214131
• NM_001864.4:c.102+3_102+8dupGGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001864.4(COX7A1):​c.102+3_102+8dupGGGGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 143,960 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 0.00026 (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+3_102+8dupGGGGGG		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+3_102+8dupGGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3
COX7A1	ENST00000589154.1	c.75+30_75+35dupGGGGGG		intron_variant	Intron 2 of 3	5		ENSP00000468063.3
COX7A1	ENST00000437291.6	c.-67+3_-67+8dupGGGGGG		splice_region_variant, intron_variant	Intron 2 of 3	3		ENSP00000475885.1
COX7A1	ENST00000481297.1	n.147_152dupGGGGGG		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 39 AN: 143846 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000416

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000430

Gnomad SAS AF: 0.000671

Gnomad FIN AF: 0.000430

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000229

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00192 AC: 360 AN: 187824 Hom.: 0 AF XY: 0.00182 AC XY: 188 AN XY: 103144

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00286

Gnomad EAS exome AF: 0.000932

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.00183

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.00185

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.000264 AC: 38 AN: 143960 Hom.: 0 Cov.: 32 AF XY: 0.000357 AC XY: 25 AN XY: 69932

Gnomad4 AFR AF: 0.000204

Gnomad4 AMR AF: 0.000416

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000432

Gnomad4 SAS AF: 0.000671

Gnomad4 FIN AF: 0.000430

Gnomad4 NFE AF: 0.000229

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00188 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;