14-70978516-G-C

Position:

• chr14-70978516-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX1	NM_014982.3	c.2179G>C	p.Glu727Gln	missense_variant	6/36	ENST00000304743.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX1	ENST00000304743.7	c.2179G>C	p.Glu727Gln	missense_variant	6/36	1	NM_014982.3	P4
PCNX1	ENST00000439984.7	c.2179G>C	p.Glu727Gln	missense_variant	6/34	1		A1
PCNX1	ENST00000554879.5	n.2625G>C		non_coding_transcript_exon_variant	6/10	1
PCNX1	ENST00000556846.1	n.139G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.2179G>C (p.E727Q) alteration is located in exon 6 (coding exon 6) of the PCNX1 gene. This alteration results from a G to C substitution at nucleotide position 2179, causing the glutamic acid (E) at amino acid position 727 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.19	T;T
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.18		Gain of helix (P = 0.062);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-71445233;