NM_014801.4:c.3019G>T

Variant names:

• chr1-233198986-C-A
• rs535193160
• NM_014801.4:c.3019G>T

Variant summary

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

The NM_014801.4(PCNX2):​c.3019G>T​(p.Val1007Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,453,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1007I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PCNX2 NM_014801.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

Genes affected

PCNX2 (HGNC:8736): (pecanex 2) This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]

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=0.039680988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.3019G>T	p.Val1007Phe	missense_variant	Exon 15 of 34	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.3019G>T	p.Val1007Phe	missense_variant	Exon 15 of 34	5	NM_014801.4	ENSP00000258229.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233686 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126694

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000945

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1453390 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 721974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000812

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.0060
DANN	Benign	0.50
DEOGEN2	Benign	0.0035	T;.;.;.
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.086	T;T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.050	N;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;N;.;N
REVEL	Benign	0.29
Sift	Benign	0.47	T;T;.;T
Sift4G	Benign	0.21	T;T;T;.
Polyphen		0.0	B;.;.;.
Vest4		0.18
MutPred		0.43		Loss of glycosylation at S1002 (P = 0.1811);.;.;.;
MVP		0.11
MPC		0.20
ClinPred		0.026	T
GERP RS		-7.8
Varity_R		0.039
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs535193160; hg19: chr1-233334732;