chr6-75243760-C-T

Variant names:

• chr6-75243760-C-T
• rs1211922332
• ENST00000370089.6:c.71G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000370089.6(COX7A2):​c.71G>A​(p.Gly24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COX7A2 ENST00000370089.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.141
• Publications: 0 publications found

Genes affected

COX7A2 (HGNC:2288): (cytochrome c oxidase subunit 7A2) Cytochrome c oxidase, 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 three catalytic subunits encoded by mitochondrial genes, and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, while the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes polypeptide 2 (liver isoform) of subunit VIIa, with this polypeptide being present in both muscle and non-muscle tissues. In addition to polypeptide 2, subunit VIIa includes polypeptide 1 (muscle isoform), which is present only in muscle tissues, and a related protein, which is present in all tissues. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4 and 14. [provided by RefSeq, Oct 2009]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07071194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370089.6. 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
	COX7A2	NM_001366293.2	MANE Select	c.-26G>A		5_prime_UTR	Exon 1 of 4	NP_001353222.1	P14406
	COX7A2	NM_001366292.3		c.-26G>A		5_prime_UTR	Exon 2 of 5	NP_001353221.2	P14406
	COX7A2	NM_001865.6		c.-26G>A		5_prime_UTR	Exon 2 of 5	NP_001856.3	P14406

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7A2	ENST00000370089.6	TSL:1	c.71G>A	p.Gly24Asp	missense	Exon 1 of 4	ENSP00000359106.2	H0UI06
	COX7A2	ENST00000684430.2	MANE Select	c.-26G>A		5_prime_UTR	Exon 1 of 4	ENSP00000506727.1	P14406
	COX7A2	ENST00000370081.6	TSL:3	c.71G>A	p.Gly24Asp	missense	Exon 2 of 5	ENSP00000359098.2	H0UI06

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.6
DANN	Benign	0.86
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.14
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.031
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.079	T
Vest4		0.21
MutPred		0.33		Loss of helix (P = 0.0626)
MVP		0.21
MPC		0.12
ClinPred		0.28	T
GERP RS		-0.11
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
gMVP		0.13
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1211922332; hg19: chr6-75953476;