7-43645337-C-T

Position:

• chr7-43645337-C-T

Variant summary

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

The NM_018224.4(COA1):​c.178G>A​(p.Ala60Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COA1 NM_018224.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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

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=0.18113658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COA1	NM_018224.4	c.178G>A	p.Ala60Thr	missense_variant	4/6	ENST00000223336.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COA1	ENST00000223336.11	c.178G>A	p.Ala60Thr	missense_variant	4/6	2	NM_018224.4	P1

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

Jan 17, 2024

The c.178G>A (p.A60T) alteration is located in exon 4 (coding exon 3) of the COA1 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the alanine (A) at amino acid position 60 to be replaced by a threonine (T). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T;.;.;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M;M;M;.;.
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.021	D;D;D;D;D
Sift4G	Uncertain	0.044	D;D;D;.;D
Polyphen		1.0	D;D;D;.;.
Vest4		0.35
MutPred		0.24		Gain of glycosylation at A60 (P = 0.0391);Gain of glycosylation at A60 (P = 0.0391);Gain of glycosylation at A60 (P = 0.0391);Gain of glycosylation at A60 (P = 0.0391);Gain of glycosylation at A60 (P = 0.0391);
MVP		0.45
MPC		0.84
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.53

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: chr7-43684936; COSMIC: COSV105036439; COSMIC: COSV105036439;