14-60115134-C-T

Position:

• chr14-60115134-C-T

Variant summary

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

The NM_001330177.2(PCNX4):​c.1030C>T​(p.Pro344Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCNX4 NM_001330177.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.308

Genes affected

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06557819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX4	NM_001330177.2	c.1030C>T	p.Pro344Ser	missense_variant	4/11	ENST00000406854.6
PCNX4	NM_022495.5	c.328C>T	p.Pro110Ser	missense_variant	3/10
PCNX4	XM_047431699.1	c.1030C>T	p.Pro344Ser	missense_variant	4/11
PCNX4	XM_047431700.1	c.1030C>T	p.Pro344Ser	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX4	ENST00000406854.6	c.1030C>T	p.Pro344Ser	missense_variant	4/11	5	NM_001330177.2	P2
PCNX4	ENST00000317623.8	c.328C>T	p.Pro110Ser	missense_variant	3/10	5		A2
PCNX4	ENST00000406949.5	c.328C>T	p.Pro110Ser	missense_variant	3/10	2
PCNX4	ENST00000556907.1	n.444-585C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

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

Aug 02, 2021

The c.328C>T (p.P110S) alteration is located in exon 3 (coding exon 2) of the PCNX4 gene. This alteration results from a C to T substitution at nucleotide position 328, causing the proline (P) at amino acid position 110 to be replaced by a serine (S). 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	Benign	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.4
DANN	Benign	0.59
DEOGEN2	Benign	0.0055	.;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.62	.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0080, 0.013	.;B;B
Vest4		0.060
MutPred		0.13		.;Gain of phosphorylation at P344 (P = 0.0662);.;
MVP		0.081
MPC		0.012
ClinPred		0.067	T
GERP RS		0.37
Varity_R		0.027
gMVP		0.22

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: rs1895819766; hg19: chr14-60581852;