12-107688682-C-T

Variant names:

• chr12-107688682-C-T
• rs148629471
• NM_007062.3:c.199C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001317963.2(PWP1):​c.-466C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: PWP1 NM_001317963.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 1 publications found

Genes affected

PWP1 (HGNC:17015): (PWP1 homolog, endonuclein) The protein encoded by this gene contains several WD-40 repeats and is found mostly in the nucleus. The expression and localization of this protein are cell cycle dependent. Expression of this gene is upregulated in pancreatic adenocarcinoma. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06737253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317963.2. 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
	PWP1	NM_007062.3	MANE Select	c.199C>T	p.Arg67Cys	missense	Exon 3 of 15	NP_008993.1	Q13610-1
	PWP1	NM_001317963.2		c.-466C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001304892.1
	PWP1	NM_001317962.2		c.13C>T	p.Arg5Cys	missense	Exon 3 of 15	NP_001304891.1	B4DJV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWP1	ENST00000412830.8	TSL:1 MANE Select	c.199C>T	p.Arg67Cys	missense	Exon 3 of 15	ENSP00000387365.3	Q13610-1
	PWP1	ENST00000920794.1		c.199C>T	p.Arg67Cys	missense	Exon 3 of 16	ENSP00000590853.1
	PWP1	ENST00000920793.1		c.199C>T	p.Arg67Cys	missense	Exon 3 of 15	ENSP00000590852.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251398 AF XY: 0.0000883

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000227 AC: 332 AN: 1461794 Hom.: 0 Cov.: 31 AF XY: 0.000195 AC XY: 142 AN XY: 727208

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000274 AC: 305 AN: 1111922

Other (OTH) AF: 0.000132 AC: 8 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74480

African (AFR) AF: 0.0000963 AC: 4 AN: 41548

American (AMR) AF: 0.000261 AC: 4 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.000166

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.024
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.20
Sift	Benign	0.047	D
Sift4G	Uncertain	0.053	T
Polyphen		0.73	P
Vest4		0.39
MVP		0.78
MPC		0.49
ClinPred		0.035	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.084
gMVP		0.11
Mutation Taster		=96/4	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: rs148629471; hg19: chr12-108082459;