Genetic Variant NM_001864.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX7A1	NM_001864.4 link	c.102+6_102+8dupGGG		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000292907.8	NP_001855.1	P24310Q6FGI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX7A1	ENST00000292907.8 link	c.102+6_102+8dupGGG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001864.4	ENSP00000292907.3		P24310

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 v4.3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over