chr20-31639012-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032609.3(COX4I2):c.1-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000914 in 1,608,486 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00092 ( 6 hom. )

Consequence

COX4I2
NM_032609.3 splice_region, intron

Scores

Splicing: ADA: 0.00003143

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.424

Variant links:

Genes affected

COX4I2 (HGNC:16232): (cytochrome c oxidase subunit 4I2) Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes isoform 2 of subunit IV. Isoform 1 of subunit IV is encoded by a different gene, however, the two genes show a similar structural organization. Subunit IV is the largest nuclear encoded subunit which plays a pivotal role in COX regulation. [provided by RefSeq, Jul 2008]

COX4I2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 20-31639012-C-T is Benign according to our data. Variant chr20-31639012-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 338031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COX4I2	NM_032609.3 link	c.1-6C>T	splice_region_variant, intron_variant	Intron 1 of 4	ENST00000376075.4	NP_115998.2	Q96KJ9H6SG14
COX4I2	XM_005260581.4 link	c.1-6C>T	splice_region_variant, intron_variant	Intron 1 of 3		XP_005260638.1
COX4I2	XM_005260579.5 link	c.-172C>T	upstream_gene_variant			XP_005260636.1
COX4I2	XM_005260580.5 link	c.-172C>T	upstream_gene_variant			XP_005260637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX4I2	ENST00000376075.4 link	c.1-6C>T		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_032609.3	ENSP00000365243.3		Q96KJ9
COX4I2	ENST00000490030.1 link	n.31-6C>T		splice_region_variant, intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00131

AC:

316

AN:

241284

Hom.:

AF XY:

0.00156

AC XY:

203

AN XY:

130168

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00297

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.000920

AC:

1340

AN:

1456234

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

783

AN XY:

723572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000980

Gnomad4 ASJ exome

AF:

0.00205

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00444

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000629

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.000854

AC:

130

AN:

152252

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000991

Hom.:

Bravo

AF:

0.000790

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

COX4I2: BP4, BS2 -

May 21, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over