chr11-66605730-G-C

Variant names:

• chr11-66605730-G-C
• rs10061
• NM_005125.2:c.700G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005125.2(CCS):​c.700G>C​(p.Ala234Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCS NM_005125.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23

Genes affected

CCS (HGNC:1613): (copper chaperone for superoxide dismutase) Copper chaperone for superoxide dismutase specifically delivers Cu to copper/zinc superoxide dismutase and may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCS	NM_005125.2	c.700G>C	p.Ala234Pro	missense_variant	Exon 8 of 8	ENST00000533244.6	NP_005116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCS	ENST00000533244.6	c.700G>C	p.Ala234Pro	missense_variant	Exon 8 of 8	1	NM_005125.2	ENSP00000436318.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.060	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.79		Loss of catalytic residue at A234 (P = 0.0109);.;.;
MVP		0.80
MPC		0.46
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.91
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 15

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

Publications

LitVar

Other links and lift over

dbSNP: rs10061; hg19: chr11-66373201;