NM_014801.4:c.3526C>T

Variant names:

• chr1-233139847-G-A
• rs188041996
• NM_014801.4:c.3526C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014801.4(PCNX2):​c.3526C>T​(p.His1176Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00307 in 1,611,472 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (10 hom.)
• Consequence: PCNX2 NM_014801.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01255244).
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.3526C>T	p.His1176Tyr	missense	Exon 20 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.3526C>T	p.His1176Tyr	missense	Exon 20 of 34	ENSP00000258229.8	A6NKB5-1
	PCNX2	ENST00000475463.6	TSL:1	n.*1016C>T		non_coding_transcript_exon	Exon 15 of 17	ENSP00000429360.1	H0YBF4
	PCNX2	ENST00000475463.6	TSL:1	n.*1016C>T		3_prime_UTR	Exon 15 of 17	ENSP00000429360.1	H0YBF4

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 152088 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00189 AC: 467 AN: 247120 AF XY: 0.00181

Gnomad AFR exome AF: 0.000908

Gnomad AMR exome AF: 0.000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000418

Gnomad NFE exome AF: 0.00355

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00317 AC: 4627 AN: 1459266 Hom.: 10 Cov.: 31 AF XY: 0.00307 AC XY: 2226 AN XY: 725828

African (AFR) AF: 0.000659 AC: 22 AN: 33366

American (AMR) AF: 0.000993 AC: 44 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26036

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85802

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00396 AC: 4399 AN: 1111038

Other (OTH) AF: 0.00201 AC: 121 AN: 60240

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152206 Hom.: 1 Cov.: 33 AF XY: 0.00202 AC XY: 150 AN XY: 74410

African (AFR) AF: 0.000818 AC: 34 AN: 41548

American (AMR) AF: 0.00118 AC: 18 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000945 AC: 10 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00382 AC: 260 AN: 67998

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00343 Hom.: 2

Bravo AF: 0.00209

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.00110 AC: 4

ESP6500EA AF: 0.00356 AC: 29

ExAC AF: 0.00165 AC: 199

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.15
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.060	T
Polyphen		0.99	D
Vest4		0.44
MVP		0.61
MPC		0.51
ClinPred		0.043	T
GERP RS		5.7
Varity_R		0.31
gMVP		0.61
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs188041996; hg19: chr1-233275593;