4-46735137-A-G

Position:

• chr4-46735137-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130902.3(COX7B2):​c.56T>C​(p.Leu19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COX7B2 NM_130902.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.331

Genes affected

COX7B2 (HGNC:24381): (cytochrome c oxidase subunit 7B2) Predicted to enable cytochrome-c oxidase activity. Predicted to be involved in electron transport chain; oxidative phosphorylation; and proton transmembrane transport. Predicted to be located in mitochondrial respirasome. Predicted to be integral component of membrane. Predicted to be part of respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17791954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX7B2	NM_130902.3	c.56T>C	p.Leu19Pro	missense_variant	3/3	ENST00000355591.8	NP_570972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX7B2	ENST00000355591.8	c.56T>C	p.Leu19Pro	missense_variant	3/3	1	NM_130902.3	ENSP00000347799.3
COX7B2	ENST00000396533.5	c.56T>C	p.Leu19Pro	missense_variant	4/4	1		ENSP00000379784.1
COX7B2	ENST00000543208.5	c.53T>C	p.Leu18Pro	missense_variant	3/3	5		ENSP00000437439.1
COX7B2	ENST00000505102.1	c.56T>C	p.Leu19Pro	missense_variant	4/4	3		ENSP00000423519.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.56T>C (p.L19P) alteration is located in exon 3 (coding exon 1) of the COX7B2 gene. This alteration results from a T to C substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.4
DANN	Benign	0.48
DEOGEN2	Benign	0.010	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.43	.;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.90	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.17	T;T;T;.
Sift4G	Benign	0.16	T;T;T;.
Polyphen		0.0	B;B;.;.
Vest4		0.23
MutPred		0.72		Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);.;Loss of helix (P = 0.0138);
MVP		0.014
MPC		0.00061
ClinPred		0.15	T
GERP RS		-3.3
Varity_R		0.071
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-46737154;