12-107710505-C-T

Variant names:

• chr12-107710505-C-T
• rs533485700
• NM_007062.3:c.1391C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_007062.3(PWP1):​c.1391C>T​(p.Ser464Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000654 in 1,558,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000071 (1 hom.)
• Consequence: PWP1 NM_007062.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• Publications: 0 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29127187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007062.3. 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.1391C>T	p.Ser464Phe	missense	Exon 14 of 15	NP_008993.1	Q13610-1
	PWP1	NM_001317962.2		c.1205C>T	p.Ser402Phe	missense	Exon 14 of 15	NP_001304891.1	B4DJV5
	PWP1	NM_001317963.2		c.755C>T	p.Ser252Phe	missense	Exon 14 of 15	NP_001304892.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWP1	ENST00000412830.8	TSL:1 MANE Select	c.1391C>T	p.Ser464Phe	missense	Exon 14 of 15	ENSP00000387365.3	Q13610-1
	PWP1	ENST00000920794.1		c.1460C>T	p.Ser487Phe	missense	Exon 15 of 16	ENSP00000590853.1
	PWP1	ENST00000920793.1		c.1382C>T	p.Ser461Phe	missense	Exon 14 of 15	ENSP00000590852.1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147606 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000436

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251170 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000709 AC: 100 AN: 1411028 Hom.: 1 Cov.: 31 AF XY: 0.0000998 AC XY: 70 AN XY: 701744

African (AFR) AF: 0.00 AC: 0 AN: 32010

American (AMR) AF: 0.0000231 AC: 1 AN: 43276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23918

East Asian (EAS) AF: 0.00 AC: 0 AN: 37032

South Asian (SAS) AF: 0.00105 AC: 90 AN: 85528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078700

Other (OTH) AF: 0.000106 AC: 6 AN: 56776

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147606 Hom.: 0 Cov.: 30 AF XY: 0.0000279 AC XY: 2 AN XY: 71580

African (AFR) AF: 0.00 AC: 0 AN: 40018

American (AMR) AF: 0.00 AC: 0 AN: 14446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4964

South Asian (SAS) AF: 0.000436 AC: 2 AN: 4588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67372

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000123 AC: 15

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000548

EpiControl AF: 0.00

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	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.016	D
Sift4G	Benign	0.30	T
Polyphen		0.94	P
Vest4		0.55
MutPred		0.43		Loss of disorder (P = 0.0368)
MVP		0.86
MPC		0.73
ClinPred		0.22	T
GERP RS		5.8
Varity_R		0.31
gMVP		0.26
Mutation Taster		=59/41	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: rs533485700; hg19: chr12-108104282;