14-71019061-G-T

Variant names:

• chr14-71019061-G-T
• rs193920949
• NM_014982.3:c.3049G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014982.3(PCNX1):​c.3049G>T​(p.Ala1017Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCNX1 NM_014982.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.60
• Publications: 1 publications found

Genes affected

PCNX1 (HGNC:19740): (pecanex 1) This gene encodes an evolutionarily conserved transmembrane protein similar to the pecanex protein in Drosophila. The fly protein is a component of the Notch signaling pathway, which functions in several developmental processes. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014982.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	NM_014982.3	MANE Select	c.3049G>T	p.Ala1017Ser	missense	Exon 12 of 36	NP_055797.2
	PCNX1	NM_001308160.2		c.2716G>T	p.Ala906Ser	missense	Exon 10 of 34	NP_001295089.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	ENST00000304743.7	TSL:1 MANE Select	c.3049G>T	p.Ala1017Ser	missense	Exon 12 of 36	ENSP00000304192.2
	PCNX1	ENST00000439984.7	TSL:1	c.2716G>T	p.Ala906Ser	missense	Exon 10 of 34	ENSP00000396617.3
	PCNX1	ENST00000554691.5	TSL:1	c.223G>T	p.Ala75Ser	missense	Exon 2 of 25	ENSP00000451016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.0	L
PhyloP100		9.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.27
Sift	Benign	0.57	T
Sift4G	Benign	0.57	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.47		Loss of catalytic residue at A1017 (P = 0.1326)
MVP		0.20
MPC		0.50
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.23
gMVP		0.64
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193920949; hg19: chr14-71485778; COSMIC: COSV53091404;