Genetic Variant COX7A1:p.Arg5Leu (chr19-36152394-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001864.4(COX7A1):c.14G>T(p.Arg5Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000996 in 1,365,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

COX7A1
NM_001864.4 missense, splice_region

Scores

Splicing: ADA: 0.005668

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15156391).

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.14G>T	p.Arg5Leu	missense splice_region	Exon 1 of 4	NP_001855.1	Q6FGI7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX7A1	ENST00000292907.8	TSL:1 MANE Select	c.14G>T	p.Arg5Leu	missense splice_region	Exon 1 of 4	ENSP00000292907.3	P24310
COX7A1	ENST00000589154.1	TSL:5	c.14G>T	p.Arg5Leu	missense splice_region	Exon 1 of 4	ENSP00000468063.3	K7ER11
COX7A1	ENST00000481297.1	TSL:2	n.56G>T		splice_region non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000593

AC:

AN:

84282

AF XY:

0.0000671

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

126

AN:

1213656

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

587990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25700

American (AMR)

AF:

0.00

AC:

AN:

19952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17752

East Asian (EAS)

AF:

0.00

AC:

AN:

29720

South Asian (SAS)

AF:

0.00

AC:

AN:

43288

European-Finnish (FIN)

AF:

0.0000234

AC:

AN:

42750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4668

European-Non Finnish (NFE)

AF:

0.000123

AC:

121

AN:

981054

Other (OTH)

AF:

0.0000820

AC:

AN:

48772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

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:

0.000153

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.0000598

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.034

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.53

M_CAP

Benign

0.048

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.76

PhyloP100

1.1

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.92

REVEL

Benign

0.19

Sift

Benign

0.25

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.30

MVP

0.21

MPC

0.58

ClinPred

0.54

GERP RS

4.1

PromoterAI

0.0026

Neutral

(source)

Varity_R

0.22

gMVP

0.67

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0057

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over