chr22-50524255-G-C

Position:

• chr22-50524255-G-C

Variant summary

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

The NM_005138.3(SCO2):​c.157C>G​(p.Gln53Glu) 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. 16/21 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: 33)
• Consequence: SCO2 NM_005138.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791

Genes affected

SCO2 (HGNC:10604): (synthesis of cytochrome C oxidase 2) Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. Human COX is a multimeric protein complex that requires several assembly factors; this gene encodes one of the COX assembly factors. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6. [provided by RefSeq, Oct 2014]

NCAPH2 (HGNC:25071): (non-SMC condensin II complex subunit H2) This gene encodes one of the non-SMC subunits of the condensin II complex. This complex plays an essential role in mitotic chromosome assembly. Alternate splicing of this gene results in multiple transcript variants.[provided by RefSeq, May 2010]

ENSG00000272821 (HGNC:):

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=0.1020475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCO2	NM_005138.3	c.157C>G	p.Gln53Glu	missense_variant	2/2	ENST00000395693.8	NP_005129.2
NCAPH2	NM_152299.4	c.*880G>C		3_prime_UTR_variant	20/20	ENST00000420993.7	NP_689512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCO2	ENST00000395693.8	c.157C>G	p.Gln53Glu	missense_variant	2/2	1	NM_005138.3	ENSP00000379046.4
NCAPH2	ENST00000420993.7	c.*880G>C		3_prime_UTR_variant	20/20	1	NM_152299.4	ENSP00000410088.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.6
DANN	Benign	0.87
DEOGEN2	Benign	0.34	T;T;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.48	.;T;.;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.15	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.50	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.039	B;B;B;B
Vest4		0.26
MutPred		0.27		Gain of catalytic residue at Q53 (P = 0.1152);Gain of catalytic residue at Q53 (P = 0.1152);Gain of catalytic residue at Q53 (P = 0.1152);Gain of catalytic residue at Q53 (P = 0.1152);
MVP		0.83
MPC		0.039
ClinPred		0.14	T
GERP RS		4.0
Varity_R		0.14
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs74315510; hg19: chr22-50962684;