Genetic Variant PIP:p.Arg118Trp (chr7-143139553-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002652.3(PIP):c.352C>T(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,612,766 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 207 hom. )

Consequence

PIP
NM_002652.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.66

Variant links:

Genes affected

PIP (HGNC:8993): (prolactin induced protein) Enables IgG binding activity; aspartic-type endopeptidase activity; and identical protein binding activity. Involved in several processes, including detection of chemical stimulus involved in sensory perception of bitter taste; negative regulation of T cell apoptotic process; and proteolysis. Located in extracellular space and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PIP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00939703).

BP6

Variant 7-143139553-C-T is Benign according to our data. Variant chr7-143139553-C-T is described in ClinVar as [Benign]. Clinvar id is 731154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP	NM_002652.3 link	c.352C>T	p.Arg118Trp	missense_variant	Exon 4 of 4	ENST00000291009.4	NP_002643.1	P12273

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP	ENST00000291009.4 link	c.352C>T	p.Arg118Trp	missense_variant	Exon 4 of 4	1	NM_002652.3	ENSP00000291009.3		P12273

Frequencies

GnomAD3 genomes

AF:

0.00683

AC:

1038

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00899

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00732

AC:

1841

AN:

251432

Hom.:

AF XY:

0.00712

AC XY:

968

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.00947

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00844

AC:

12333

AN:

1460648

Hom.:

207

Cov.:

AF XY:

0.00812

AC XY:

5904

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.00728

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.0234

Gnomad4 NFE exome

AF:

0.00919

Gnomad4 OTH exome

AF:

0.00724

GnomAD4 genome

AF:

0.00682

AC:

1038

AN:

152118

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

539

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.00899

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00822

Hom.:

Bravo

AF:

0.00546

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00754

AC:

916

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00791

EpiControl

AF:

0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.28

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0094

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.097

Sift

Benign

0.050

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.19

MVP

0.34

MPC

0.34

ClinPred

0.068

GERP RS

-4.8

Varity_R

0.41

gMVP

0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over