rs144214406

Variant names:

• chr2-219172848-G-A
• rs144214406
• NM_015680.6:c.971C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-219172848-G-A
• chr2-219172848-G-C
• chr2-219172848-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015680.6(CNPPD1):​c.971C>T​(p.Pro324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P324R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

Genes affected

CNPPD1 (HGNC:25220): (cyclin Pas1/PHO80 domain containing 1) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be integral component of membrane. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08609095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPPD1	NM_015680.6	c.971C>T	p.Pro324Leu	missense_variant	Exon 8 of 8	ENST00000360507.10	NP_056495.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNPPD1	ENST00000360507.10	c.971C>T	p.Pro324Leu	missense_variant	Exon 8 of 8	1	NM_015680.6	ENSP00000353698.5
CNPPD1	ENST00000409789.5	c.971C>T	p.Pro324Leu	missense_variant	Exon 9 of 9	1		ENSP00000386277.1
CNPPD1	ENST00000453038.5	c.*46C>T		downstream_gene_variant		2		ENSP00000410109.1
CNPPD1	ENST00000451647.1	c.*203C>T		downstream_gene_variant		3		ENSP00000405997.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

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	Benign	0.085
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-0.049
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.043
Sift	Benign	0.052	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.44	B;B
Vest4		0.26
MutPred		0.18		Loss of glycosylation at P324 (P = 0.0045);Loss of glycosylation at P324 (P = 0.0045);
MVP		0.25
MPC		0.78
ClinPred		0.78	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144214406; hg19: chr2-220037570;