NM_005125.2:c.307G>T

Variant names:

• chr11-66599515-G-T
• rs201630725
• NM_005125.2:c.307G>T

Variant summary

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

The NM_005125.2(CCS):​c.307G>T​(p.Val103Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCS NM_005125.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCS	NM_005125.2	c.307G>T	p.Val103Leu	missense_variant	Exon 4 of 8	ENST00000533244.6	NP_005116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCS	ENST00000533244.6	c.307G>T	p.Val103Leu	missense_variant	Exon 4 of 8	1	NM_005125.2	ENSP00000436318.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000436 AC: 1 AN: 229582 Hom.: 0 AF XY: 0.00000800 AC XY: 1 AN XY: 125076

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432416 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 710700

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.24
Sift	Benign	0.038	D;D
Sift4G	Benign	0.074	T;T
Polyphen		0.91	P;.
Vest4		0.56
MutPred		0.59		Loss of sheet (P = 0.1398);.;
MVP		0.50
MPC		0.45
ClinPred		0.87	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		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: rs201630725; hg19: chr11-66366986;