rs1043160

Positions:

• chr2-219173034-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015680.6(CNPPD1):​c.785T>C​(p.Ile262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,612,714 control chromosomes in the GnomAD database, including 276,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.50 (20253 hom., cov: 31)
  • Exomes 𝑓: 0.59 (256164 hom.)
• Consequence: CNPPD1 NM_015680.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.320183E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPPD1	NM_015680.6	c.785T>C	p.Ile262Thr	missense_variant	8/8	ENST00000360507.10	NP_056495.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNPPD1	ENST00000360507.10	c.785T>C	p.Ile262Thr	missense_variant	8/8	1	NM_015680.6	ENSP00000353698	P1
CNPPD1	ENST00000409789.5	c.785T>C	p.Ile262Thr	missense_variant	9/9	1		ENSP00000386277	P1
CNPPD1	ENST00000453038.5	c.785T>C	p.Ile262Thr	missense_variant	9/9	2		ENSP00000410109
CNPPD1	ENST00000451647.1			downstream_gene_variant		3		ENSP00000405997

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75507 AN: 151794 Hom.: 20256 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.503

GnomAD3 exomes AF: 0.533 AC: 132948 AN: 249246 Hom.: 37467 AF XY: 0.549 AC XY: 74006 AN XY: 134860

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.613

Gnomad EAS exome AF: 0.272

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.612

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.586 AC: 856021 AN: 1460802 Hom.: 256164 Cov.: 60 AF XY: 0.588 AC XY: 426963 AN XY: 726654

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.497 AC: 75529 AN: 151912 Hom.: 20253 Cov.: 31 AF XY: 0.499 AC XY: 37034 AN XY: 74234

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.497

Alfa AF: 0.584 Hom.: 59311

Bravo AF: 0.471

TwinsUK AF: 0.607 AC: 2251

ALSPAC AF: 0.610 AC: 2352

ESP6500AA AF: 0.311 AC: 1370

ESP6500EA AF: 0.609 AC: 5239

ExAC AF: 0.540 AC: 65508

Asia WGS AF: 0.344 AC: 1198 AN: 3478

EpiCase AF: 0.606

EpiControl AF: 0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.4
DANN	Benign	0.52
DEOGEN2	Benign	0.00076	T;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.12	.;T;T
MetaRNN	Benign	0.000013	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.75	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.62	T;T;T
Sift4G	Benign	0.68	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.0070
MPC		0.29
ClinPred		0.00050	T
GERP RS		2.2
Varity_R		0.018
gMVP		0.12

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: rs1043160; hg19: chr2-220037756; COSMIC: COSV55407502; COSMIC: COSV55407502;