14-60125690-T-A

Position:

• chr14-60125690-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330177.2(PCNX4):​c.3134T>A​(p.Phe1045Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: 3.69

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 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=0.26653677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX4	NM_001330177.2	c.3134T>A	p.Phe1045Tyr	missense_variant	10/11	ENST00000406854.6
PCNX4	NM_022495.5	c.2432T>A	p.Phe811Tyr	missense_variant	9/10
PCNX4	XM_047431699.1	c.3134T>A	p.Phe1045Tyr	missense_variant	10/11
PCNX4	XM_047431700.1	c.*30T>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX4	ENST00000406854.6	c.3134T>A	p.Phe1045Tyr	missense_variant	10/11	5	NM_001330177.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jul 20, 2021

The c.2432T>A (p.F811Y) alteration is located in exon 9 (coding exon 8) of the PCNX4 gene. This alteration results from a T to A substitution at nucleotide position 2432, causing the phenylalanine (F) at amino acid position 811 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.012	.;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.94	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.98, 1.0	.;D;D
Vest4		0.49
MutPred		0.53		.;Gain of loop (P = 0.024);.;
MVP		0.11
MPC		0.017
ClinPred		0.76	D
GERP RS		5.0
Varity_R		0.15
gMVP		0.35

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: chr14-60592408;