Genetic Variant NM_015680.6:c.946C>A (chr2-219172873-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015680.6(CNPPD1):c.946C>A(p.Leu316Met) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L316Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CNPPD1
NM_015680.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Publications

0 publications found

Variant links:

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]

CNPPD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17054689).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPPD1	NM_015680.6	MANE Select	c.946C>A	p.Leu316Met	missense	Exon 8 of 8	NP_056495.4
CNPPD1	NM_001321389.2		c.946C>A	p.Leu316Met	missense	Exon 9 of 9	NP_001308318.2	Q9BV87
CNPPD1	NM_001321390.2		c.946C>A	p.Leu316Met	missense	Exon 9 of 9	NP_001308319.2	Q9BV87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPPD1	ENST00000360507.10	TSL:1 MANE Select	c.946C>A	p.Leu316Met	missense	Exon 8 of 8	ENSP00000353698.5	Q9BV87
CNPPD1	ENST00000409789.5	TSL:1	c.946C>A	p.Leu316Met	missense	Exon 9 of 9	ENSP00000386277.1	Q9BV87
CNPPD1	ENST00000874465.1		c.1027C>A	p.Leu343Met	missense	Exon 8 of 8	ENSP00000544524.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000423

AC:

AN:

236656

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

Eigen

Benign

0.0041

Eigen_PC

Benign

-0.047

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.65

M_CAP

Benign

0.0051

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.69

REVEL

Benign

0.074

Sift

Benign

0.11

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.26

MutPred

0.13

Loss of glycosylation at S315 (P = 0.0484)

MVP

0.36

MPC

0.71

ClinPred

0.37

GERP RS

0.95

Varity_R

0.060

gMVP

0.39

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over