NM_015680.6:c.824G>T

Variant names:

• chr2-219172995-C-A
• rs201528705
• NM_015680.6:c.824G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015680.6(CNPPD1):​c.824G>T​(p.Arg275Leu) 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. 15/21 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. R275C) 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: 0.238

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052118897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNPPD1	NM_015680.6	c.824G>T	p.Arg275Leu	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.824G>T	p.Arg275Leu	missense_variant	Exon 8 of 8	1	NM_015680.6	ENSP00000353698.5
CNPPD1	ENST00000409789.5	c.824G>T	p.Arg275Leu	missense_variant	Exon 9 of 9	1		ENSP00000386277.1
CNPPD1	ENST00000453038.5	c.824G>T	p.Arg275Leu	missense_variant	Exon 9 of 9	2		ENSP00000410109.1
CNPPD1	ENST00000451647.1	c.*56G>T		downstream_gene_variant		3		ENSP00000405997.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.0
DANN	Benign	0.90
DEOGEN2	Benign	0.0034	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.32	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.30	T;T;.
Polyphen		0.012	B;B;.
Vest4		0.072
MutPred		0.32		Loss of disorder (P = 0.0951);Loss of disorder (P = 0.0951);Loss of disorder (P = 0.0951);
MVP		0.12
MPC		0.29
ClinPred		0.051	T
GERP RS		0.63
Varity_R		0.035
gMVP		0.29

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: rs201528705; hg19: chr2-220037717;