chr12-107708927-C-T

Variant names:

• chr12-107708927-C-T
• rs142592988
• NM_007062.3:c.1079C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007062.3(PWP1):​c.1079C>T​(p.Ala360Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000246 in 1,612,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: PWP1 NM_007062.3 missense, splice_region
• Scores: Splicing: ADA: 0.2644
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10331884).

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.1079C>T	p.Ala360Val	missense splice_region	Exon 12 of 15	NP_008993.1	Q13610-1
	PWP1	NM_001317962.2		c.893C>T	p.Ala298Val	missense splice_region	Exon 12 of 15	NP_001304891.1	B4DJV5
	PWP1	NM_001317963.2		c.443C>T	p.Ala148Val	missense splice_region	Exon 12 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.1079C>T	p.Ala360Val	missense splice_region	Exon 12 of 15	ENSP00000387365.3	Q13610-1
	PWP1	ENST00000920794.1		c.1148C>T	p.Ala383Val	missense splice_region	Exon 13 of 16	ENSP00000590853.1
	PWP1	ENST00000920793.1		c.1070C>T	p.Ala357Val	missense splice_region	Exon 12 of 15	ENSP00000590852.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000215 AC: 54 AN: 250868 AF XY: 0.000162

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000726

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000251 AC: 366 AN: 1460434 Hom.: 0 Cov.: 31 AF XY: 0.000233 AC XY: 169 AN XY: 726580

African (AFR) AF: 0.000150 AC: 5 AN: 33444

American (AMR) AF: 0.000762 AC: 34 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5160

European-Non Finnish (NFE) AF: 0.000271 AC: 301 AN: 1111568

Other (OTH) AF: 0.000315 AC: 19 AN: 60272

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.000852 AC: 13 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68024

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000272

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000382

EpiControl AF: 0.000296

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	0.25
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-0.00064
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.13
Sift	Benign	0.62	T
Sift4G	Benign	1.0	T
Polyphen		0.58	P
Vest4		0.35
MVP		0.32
MPC		0.29
ClinPred		0.035	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.66
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.26
dbscSNV1_RF	Benign	0.53
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: rs142592988; hg19: chr12-108102704;