Genetic Variant NM_004718.4:c.*555_*556insGTGTGTATTT (chr2-42350663-T-TAAATACACAC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004718.4(COX7A2L):c.*555_*556insGTGTGTATTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 28678 hom., cov: 0)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

COX7A2L
NM_004718.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.600

Publications

12 publications found

Variant links:

Genes affected

COX7A2L (HGNC:2289): (cytochrome c oxidase subunit 7A2 like) 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 a protein similar to polypeptides 1 and 2 of subunit VIIa in the C-terminal region, and also highly similar to the mouse Sig81 protein sequence. This gene is expressed in all tissues, and upregulated in a breast cancer cell line after estrogen treatment. It is possible that this gene represents a regulatory subunit of COX and mediates the higher level of energy production in target cells by estrogen. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

COX7A2L links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX7A2L	NM_004718.4 link	c.555_556insGTGTGTATTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000234301.3	NP_004709.2	O14548Q6FGA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX7A2L	ENST00000234301.3 link	c.555_556insGTGTGTATTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_004718.4	ENSP00000234301.2		O14548

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92201

AN:

151420

Hom.:

28638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.587

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.609

AC:

92299

AN:

151540

Hom.:

28678

Cov.:

AF XY:

0.607

AC XY:

44951

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.705

AC:

29136

AN:

41306

American (AMR)

AF:

0.452

AC:

6889

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2004

AN:

3460

East Asian (EAS)

AF:

0.742

AC:

3798

AN:

5120

South Asian (SAS)

AF:

0.562

AC:

2705

AN:

4812

European-Finnish (FIN)

AF:

0.622

AC:

6563

AN:

10552

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.581

AC:

39339

AN:

67752

Other (OTH)

AF:

0.584

AC:

1227

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1791

3582

5374

7165

8956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.459

Hom.:

971

Asia WGS

AF:

0.606

AC:

2106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_004718.4:c.555_556insGTGTGTATTT

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