1-233025206-G-C

Variant names:

• chr1-233025206-G-C
• rs201941744
• NM_014801.4:c.4545C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014801.4(PCNX2):​c.4545C>G​(p.Asn1515Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1515N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PCNX2 NM_014801.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.4545C>G	p.Asn1515Lys	missense_variant	Exon 26 of 34	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.4545C>G	p.Asn1515Lys	missense_variant	Exon 26 of 34	5	NM_014801.4	ENSP00000258229.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249296 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135196

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727132

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.15
Sift	Benign	0.057	T;T
Sift4G	Uncertain	0.015	D;T
Polyphen		0.99	D;D
Vest4		0.87
MutPred		0.28		Gain of ubiquitination at N1515 (P = 0.0162);.;
MVP		0.41
MPC		0.24
ClinPred		0.91	D
GERP RS		-1.7
Varity_R		0.47
gMVP		0.80

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: rs201941744; hg19: chr1-233160952;