NM_014801.4:c.2929A>C

Variant names:

• chr1-233200199-T-G
• rs200562385
• NM_014801.4:c.2929A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014801.4(PCNX2):​c.2929A>C​(p.Thr977Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T977A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCNX2 NM_014801.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

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]

ENSG00000298828 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21816182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014801.4. 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
	PCNX2	NM_014801.4	MANE Select	c.2929A>C	p.Thr977Pro	missense	Exon 14 of 34	NP_055616.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX2	ENST00000258229.14	TSL:5 MANE Select	c.2929A>C	p.Thr977Pro	missense	Exon 14 of 34	ENSP00000258229.8	A6NKB5-1
	PCNX2	ENST00000475463.6	TSL:1	n.*419A>C		non_coding_transcript_exon	Exon 9 of 17	ENSP00000429360.1	H0YBF4
	PCNX2	ENST00000475463.6	TSL:1	n.*419A>C		3_prime_UTR	Exon 9 of 17	ENSP00000429360.1	H0YBF4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443644 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716104

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33188

American (AMR) AF: 0.00 AC: 0 AN: 42026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39214

South Asian (SAS) AF: 0.00 AC: 0 AN: 82666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102732

Other (OTH) AF: 0.00 AC: 0 AN: 59834

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	0.0019	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.13	B
Vest4		0.61
MutPred		0.47		Loss of helix (P = 0.1706)
MVP		0.40
MPC		0.23
ClinPred		0.65	D
GERP RS		1.6
Varity_R		0.42
gMVP		0.86
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs200562385; hg19: chr1-233335945;