chr2-219172695-G-T

Variant names:

• chr2-219172695-G-T
• rs760364743
• NM_015680.6:c.1124C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015680.6(CNPPD1):​c.1124C>A​(p.Pro375His) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29636577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015680.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPPD1	NM_015680.6	MANE Select	c.1124C>A	p.Pro375His	missense	Exon 8 of 8	NP_056495.4
	CNPPD1	NM_001321389.2		c.1124C>A	p.Pro375His	missense	Exon 9 of 9	NP_001308318.2	Q9BV87
	CNPPD1	NM_001321390.2		c.1124C>A	p.Pro375His	missense	Exon 9 of 9	NP_001308319.2	Q9BV87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNPPD1	ENST00000360507.10	TSL:1 MANE Select	c.1124C>A	p.Pro375His	missense	Exon 8 of 8	ENSP00000353698.5	Q9BV87
	CNPPD1	ENST00000409789.5	TSL:1	c.1124C>A	p.Pro375His	missense	Exon 9 of 9	ENSP00000386277.1	Q9BV87
	CNPPD1	ENST00000874465.1		c.1205C>A	p.Pro402His	missense	Exon 8 of 8	ENSP00000544524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.33
MutPred		0.50		Loss of glycosylation at P375 (P = 0.0258)
MVP		0.38
MPC		0.54
ClinPred		0.47	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.095
gMVP		0.67
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs760364743; hg19: chr2-220037417;