NM_014801.4:c.2913A>T

Variant names:

• chr1-233200215-T-A
• rs370350779
• NM_014801.4:c.2913A>T

Variant summary

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

The NM_014801.4(PCNX2):​c.2913A>T​(p.Gln971His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCNX2 NM_014801.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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.2913A>T	p.Gln971His	missense_variant	Exon 14 of 34	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.2913A>T	p.Gln971His	missense_variant	Exon 14 of 34	5	NM_014801.4	ENSP00000258229.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Uncertain	-0.064	T
MutationAssessor	Pathogenic	3.1	M;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.7	D;D;.;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;D;.;D
Sift4G	Uncertain	0.0020	D;D;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.94
MutPred		0.26		Loss of loop (P = 0.2897);.;.;.;
MVP		0.84
MPC		0.62
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.42
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs370350779; hg19: chr1-233335961;