14-60115134-C-T

Variant names:

• chr14-60115134-C-T
• rs1895819766
• NM_001330177.2:c.1030C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330177.2. 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
	PCNX4	NM_001330177.2	MANE Select	c.1030C>T	p.Pro344Ser	missense	Exon 4 of 11	NP_001317106.1	Q63HM2
	PCNX4	NM_022495.5		c.328C>T	p.Pro110Ser	missense	Exon 3 of 10	NP_071940.4	Q63HM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX4	ENST00000406854.6	TSL:5 MANE Select	c.1030C>T	p.Pro344Ser	missense	Exon 4 of 11	ENSP00000384801.1	Q63HM2
	PCNX4	ENST00000868338.1		c.1030C>T	p.Pro344Ser	missense	Exon 4 of 11	ENSP00000538397.1
	PCNX4	ENST00000317623.8	TSL:5	c.328C>T	p.Pro110Ser	missense	Exon 3 of 10	ENSP00000317396.4	B6ZDM2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	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
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.62	N
PhyloP100		0.31
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.022
Sift	Benign	0.16	T
Sift4G	Benign	0.19	T
Polyphen		0.0080	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
Mutation Taster		=94/6	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

dbSNP: rs1895819766; hg19: chr14-60581852;