rs374948695

Variant names:

• chr16-12664990-C-A
• rs374948695
• NM_018340.3:c.841G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-12664990-C-A
• chr16-12664990-C-G
• chr16-12664990-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018340.3(CPPED1):​c.841G>T​(p.Val281Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V281M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPPED1 NM_018340.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71

Genes affected

CPPED1 (HGNC:25632): (calcineurin like phosphoesterase domain containing 1) Predicted to enable metal ion binding activity; protein serine phosphatase activity; and protein threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26753706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPPED1	NM_018340.3	c.841G>T	p.Val281Leu	missense_variant	Exon 4 of 4	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2	c.415G>T	p.Val139Leu	missense_variant	Exon 3 of 3		NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9	c.841G>T	p.Val281Leu	missense_variant	Exon 4 of 4	1	NM_018340.3	ENSP00000371193.4
CPPED1	ENST00000433677.6	c.415G>T	p.Val139Leu	missense_variant	Exon 3 of 3	1		ENSP00000411127.2
CPPED1	ENST00000261660.4	c.320G>T	p.Arg107Leu	missense_variant	Exon 3 of 3	2		ENSP00000261660.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.27	T
MetaSVM	Pathogenic	1.1	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.17
MutPred		0.28		Loss of MoRF binding (P = 6e-04);
MVP		0.46
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs374948695; hg19: chr16-12758847;