Genetic Variant COX7A1:c.102+6_102+8dupGGG (chr19-36151660-A-ACCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001864.4(COX7A1):c.102+6_102+8dupGGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 143,988 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 0.0044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COX7A1
NM_001864.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0720

Publications

3 publications found

Variant links:

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]

COX7A1 links:

ENSG00000294115 (HGNC:):

ENSG00000294115 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7A1	NM_001864.4	MANE Select	c.102+6_102+8dupGGG		splice_region intron	N/A	NP_001855.1	Q6FGI7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COX7A1	ENST00000292907.8	TSL:1 MANE Select	c.102+6_102+8dupGGG	splice_region intron	N/A	ENSP00000292907.3	P24310
COX7A1	ENST00000589154.1	TSL:5	c.75+33_75+35dupGGG	intron	N/A	ENSP00000468063.3	K7ER11
COX7A1	ENST00000437291.6	TSL:3	c.-67+6_-67+8dupGGG	splice_region intron	N/A	ENSP00000475885.1	U3KQH8

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

631

AN:

143872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00397

Gnomad AMI

AF:

0.00233

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00298

Gnomad EAS

AF:

0.00407

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00527

Gnomad OTH

AF:

0.00308

GnomAD2 exomes

AF:

0.00517

AC:

971

AN:

187824

AF XY:

0.00478

show subpopulations

Gnomad AFR exome

AF:

0.00364

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00332

Gnomad EAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00333

Gnomad OTH exome

AF:

0.00678

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1061634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

533716

African (AFR)

AF:

0.00

AC:

AN:

26298

American (AMR)

AF:

0.00

AC:

AN:

33734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20064

East Asian (EAS)

AF:

0.00

AC:

AN:

27714

South Asian (SAS)

AF:

0.00

AC:

AN:

74436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4346

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

788310

Other (OTH)

AF:

0.00

AC:

AN:

44042

GnomAD4 genome

AF:

0.00438

AC:

631

AN:

143988

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

272

AN XY:

69956

show subpopulations

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

African (AFR)

AF:

0.00395

AC:

155

AN:

39204

American (AMR)

AF:

0.00451

AC:

AN:

14410

Ashkenazi Jewish (ASJ)

AF:

0.00298

AC:

AN:

3358

East Asian (EAS)

AF:

0.00409

AC:

AN:

4648

South Asian (SAS)

AF:

0.00290

AC:

AN:

4482

European-Finnish (FIN)

AF:

0.00172

AC:

AN:

9320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00527

AC:

345

AN:

65448

Other (OTH)

AF:

0.00304

AC:

AN:

1972

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.305

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00460

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.072

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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19-36151660-AC-ACCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over