3-45085699-C-T

Position:

• chr3-45085699-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_022842.5(CDCP1):​c.2450G>A​(p.Ser817Asn) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDCP1 NM_022842.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

Genes affected

CDCP1 (HGNC:24357): (CUB domain containing protein 1) This gene encodes a transmembrane protein which contains three extracellular CUB domains and acts as a substrate for Src family kinases. The protein plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03981495).
• BP6: Variant 3-45085699-C-T is Benign according to our data. Variant chr3-45085699-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3141047.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP1	NM_022842.5	c.2450G>A	p.Ser817Asn	missense_variant	9/9	ENST00000296129.6	NP_073753.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP1	ENST00000296129.6	c.2450G>A	p.Ser817Asn	missense_variant	9/9	1	NM_022842.5	ENSP00000296129	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.66
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.024
Sift	Benign	0.96	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.021
MutPred		0.11		Gain of glycosylation at T821 (P = 0.0173);
MVP		0.26
MPC		0.27
ClinPred		0.035	T
GERP RS		-3.8
Varity_R		0.017
gMVP		0.070

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: rs1698176388; hg19: chr3-45127191;