rs1331010335

Variant names:

• chr11-66599209-C-A
• NM_005125.2:c.206C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66599209-C-A
• chr11-66599209-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005125.2(CCS):​c.206C>A​(p.Thr69Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCS NM_005125.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCS	NM_005125.2	c.206C>A	p.Thr69Lys	missense_variant	Exon 3 of 8	ENST00000533244.6	NP_005116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCS	ENST00000533244.6	c.206C>A	p.Thr69Lys	missense_variant	Exon 3 of 8	1	NM_005125.2	ENSP00000436318.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461088 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726874

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.84	D;.
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.73		Gain of ubiquitination at T69 (P = 0.0085);.;
MVP		0.97
MPC		1.0
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr11-66366680;