NM_014982.3:c.2179G>C

Variant names:

• chr14-70978516-G-C
• NM_014982.3:c.2179G>C

Variant summary

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

The NM_014982.3(PCNX1):​c.2179G>C​(p.Glu727Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PCNX1 NM_014982.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.36
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3101079).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	NM_014982.3	MANE Select	c.2179G>C	p.Glu727Gln	missense	Exon 6 of 36	NP_055797.2	Q96RV3-1
	PCNX1	NM_001308160.2		c.2179G>C	p.Glu727Gln	missense	Exon 6 of 34	NP_001295089.1	Q96RV3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	ENST00000304743.7	TSL:1 MANE Select	c.2179G>C	p.Glu727Gln	missense	Exon 6 of 36	ENSP00000304192.2	Q96RV3-1
	PCNX1	ENST00000439984.7	TSL:1	c.2179G>C	p.Glu727Gln	missense	Exon 6 of 34	ENSP00000396617.3	Q96RV3-4
	PCNX1	ENST00000554879.5	TSL:1	n.2625G>C		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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	Uncertain	0.48
BayesDel_addAF	Benign	-0.0059	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	M
PhyloP100		9.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.18		Gain of helix (P = 0.062)
MVP		0.14
MPC		0.51
ClinPred		0.85	D
GERP RS		5.6
Varity_R		0.22
gMVP		0.37
Mutation Taster		=79/21	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

hg19: chr14-71445233;