rs374136858

Variant names:

• chr16-12704627-C-A
• rs374136858
• NM_018340.3:c.712G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-12704627-C-A
• chr16-12704627-C-T

Variant summary

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

The NM_018340.3(CPPED1):​c.712G>T​(p.Ala238Ser) 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 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: CPPED1 NM_018340.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPPED1	NM_018340.3	c.712G>T	p.Ala238Ser	missense_variant	Exon 3 of 4	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2	c.290-39512G>T		intron_variant	Intron 2 of 2		NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9	c.712G>T	p.Ala238Ser	missense_variant	Exon 3 of 4	1	NM_018340.3	ENSP00000371193.4
CPPED1	ENST00000433677.6	c.290-39512G>T		intron_variant	Intron 2 of 2	1		ENSP00000411127.2
CPPED1	ENST00000261660.4	c.290-39607G>T		intron_variant	Intron 2 of 2	2		ENSP00000261660.4

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	Benign	0.11
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.38
Sift	Benign	0.071	T
Sift4G	Benign	0.11	T
Polyphen		0.91	P
Vest4		0.74
MutPred		0.65		Gain of glycosylation at A238 (P = 0.0473);
MVP		0.63
MPC		0.30
ClinPred		0.96	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.35

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: rs374136858; hg19: chr16-12798484;