chr19-36151546-C-T

Variant names:

• chr19-36151546-C-T
• NM_001864.4:c.103G>A

Variant summary

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

The NM_001864.4(COX7A1):​c.103G>A​(p.Glu35Lys) variant causes a missense, splice region 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COX7A1 NM_001864.4 missense, splice_region
• Scores: Splicing: ADA: 0.9555
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

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]

ENSG00000294115 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.103G>A	p.Glu35Lys	missense splice_region	Exon 3 of 4	NP_001855.1	Q6FGI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX7A1	ENST00000292907.8	TSL:1 MANE Select	c.103G>A	p.Glu35Lys	missense splice_region	Exon 3 of 4	ENSP00000292907.3	P24310
	COX7A1	ENST00000589154.1	TSL:5	c.76G>A	p.Glu26Lys	missense splice_region	Exon 3 of 4	ENSP00000468063.3	K7ER11
	COX7A1	ENST00000437291.6	TSL:3	c.-66G>A		splice_region	Exon 3 of 4	ENSP00000475885.1	U3KQH8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.059
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.7
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.11
Sift	Benign	0.42	T
Sift4G	Benign	0.16	T
Polyphen		0.018	B
Vest4		0.21
MutPred		0.55		Gain of methylation at E35 (P = 0.0026)
MVP		0.43
MPC		1.0
ClinPred		0.89	D
GERP RS		3.2
PromoterAI		0.0012	Neutral
Varity_R		0.17
gMVP		0.45
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.96
dbscSNV1_RF	Pathogenic	0.74
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.42		Position offset: 0

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

Other links and lift over

hg19: chr19-36642448;