1-52687760-T-C

Variant names:

• chr1-52687760-T-C
• rs443751
• NM_023077.3:c.656A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1 BP4_Strong BP6_Very_Strong BA1

The NM_023077.3(COA7):​c.656A>G​(p.Lys219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,614,068 control chromosomes in the GnomAD database, including 94,528 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6885 hom., cov: 33)
  • Exomes 𝑓: 0.34 (87643 hom.)
• Consequence: COA7 NM_023077.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.99
• Publications: 36 publications found

Genes affected

COA7 (HGNC:25716): (cytochrome c oxidase assembly factor 7) Located in mitochondrial intermembrane space and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COA7 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• PM1: In a chain Cytochrome c oxidase assembly factor 7 (size 229) in uniprot entity COA7_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_023077.3
• BP4: Computational evidence support a benign effect (MetaRNN=0.0017867088).
• BP6: Variant 1-52687760-T-C is Benign according to our data. Variant chr1-52687760-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COA7	NM_023077.3	c.656A>G	p.Lys219Arg	missense_variant	Exon 3 of 3	ENST00000371538.5	NP_075565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COA7	ENST00000371538.5	c.656A>G	p.Lys219Arg	missense_variant	Exon 3 of 3	1	NM_023077.3	ENSP00000360593.3
COA7	ENST00000486918.1	n.710A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43441 AN: 152108 Hom.: 6886 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.287 AC: 72192 AN: 251300 AF XY: 0.297

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.0192

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.338 AC: 493802 AN: 1461840 Hom.: 87643 Cov.: 54 AF XY: 0.338 AC XY: 245716 AN XY: 727224

African (AFR) AF: 0.185 AC: 6208 AN: 33480

American (AMR) AF: 0.168 AC: 7492 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8892 AN: 26136

East Asian (EAS) AF: 0.0174 AC: 690 AN: 39700

South Asian (SAS) AF: 0.319 AC: 27517 AN: 86254

European-Finnish (FIN) AF: 0.347 AC: 18560 AN: 53418

Middle Eastern (MID) AF: 0.303 AC: 1747 AN: 5768

European-Non Finnish (NFE) AF: 0.363 AC: 403378 AN: 1111976

Other (OTH) AF: 0.320 AC: 19318 AN: 60386

GnomAD4 genome AF: 0.285 AC: 43449 AN: 152228 Hom.: 6885 Cov.: 33 AF XY: 0.281 AC XY: 20890 AN XY: 74414

African (AFR) AF: 0.193 AC: 8027 AN: 41540

American (AMR) AF: 0.236 AC: 3609 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3472

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5184

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4828

European-Finnish (FIN) AF: 0.347 AC: 3680 AN: 10606

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24526 AN: 67986

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.330 Hom.: 41731

Bravo AF: 0.271

TwinsUK AF: 0.378 AC: 1400

ALSPAC AF: 0.354 AC: 1366

ESP6500AA AF: 0.200 AC: 879

ESP6500EA AF: 0.355 AC: 3053

ExAC AF: 0.293 AC: 35559

Asia WGS AF: 0.163 AC: 570 AN: 3478

EpiCase AF: 0.361

EpiControl AF: 0.353

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.072
Sift	Benign	0.28	T
Sift4G	Benign	0.43	T
Polyphen		0.0060	B
Vest4		0.11
MPC		0.12
ClinPred		0.0051	T
GERP RS		5.5
Varity_R		0.040
gMVP		0.32
Mutation Taster		=81/19	polymorphism (auto)

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: rs443751; hg19: chr1-53153432; COSMIC: COSV65299123;