chr7-43647552-A-T

Variant names:

• chr7-43647552-A-T
• rs758413436
• NM_018224.4:c.98T>A

Variant summary

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

The NM_018224.4(COA1):​c.98T>A​(p.Val33Glu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COA1 NM_018224.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

COA1 (HGNC:21868): (cytochrome c oxidase assembly factor 1) Involved in mitochondrial cytochrome c oxidase assembly and mitochondrial respiratory chain complex I assembly. Located in cytosol and mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

STK17A (HGNC:11395): (serine/threonine kinase 17a) This gene is a member of the DAP kinase-related apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. The protein has apoptosis-inducing activity. [provided by RefSeq, Jul 2008]

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=0.20443943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018224.4. 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
	COA1	NM_018224.4	MANE Select	c.98T>A	p.Val33Glu	missense	Exon 3 of 6	NP_060694.2	Q9GZY4
	COA1	NM_001321197.2		c.98T>A	p.Val33Glu	missense	Exon 4 of 7	NP_001308126.1	Q9GZY4
	COA1	NM_001321198.2		c.98T>A	p.Val33Glu	missense	Exon 4 of 7	NP_001308127.1	Q9GZY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COA1	ENST00000223336.11	TSL:2 MANE Select	c.98T>A	p.Val33Glu	missense	Exon 3 of 6	ENSP00000223336.6	Q9GZY4
	COA1	ENST00000395879.5	TSL:1	c.98T>A	p.Val33Glu	missense	Exon 2 of 5	ENSP00000379218.1	Q9GZY4
	COA1	ENST00000418140.5	TSL:1	c.98T>A	p.Val33Glu	missense	Exon 4 of 4	ENSP00000410365.1	F2Z2J3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.031	D
Polyphen		0.85	P
Vest4		0.57
MutPred		0.55		Loss of sheet (P = 0.0228)
MVP		0.29
MPC		0.80
ClinPred		0.54	D
GERP RS		2.3
Varity_R		0.16
gMVP		0.51
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs758413436; hg19: chr7-43687151;