Variant chr17-68452981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017983.7(WIPI1):c.92C>T(p.Thr31Ile) variant causes a missense change. The variant allele was found at a frequency of 0.765 in 1,611,838 control chromosomes in the GnomAD database, including 473,991 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.78 ( 46068 hom., cov: 31)

Exomes 𝑓: 0.76 ( 427923 hom. )

Consequence

WIPI1
NM_017983.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.41

Variant links:

Genes affected

WIPI1 (HGNC:25471): (WD repeat domain, phosphoinositide interacting 1) This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

WIPI1 links:

PRKAR1A (HGNC:9388): (protein kinase cAMP-dependent type I regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]

PRKAR1A links:

ENSG00000267009 (HGNC:):

ENSG00000267009 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.61811E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPI1	NM_017983.7 link	c.92C>T	p.Thr31Ile	missense_variant	2/13	ENST00000262139.10	NP_060453.3	Q5MNZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPI1	ENST00000262139.10 link	c.92C>T	p.Thr31Ile	missense_variant	2/13	1	NM_017983.7	ENSP00000262139.4		Q5MNZ9-1

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117822

AN:

151970

Hom.:

46017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.844

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.701

Gnomad ASJ

AF:

0.772

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.762

GnomAD3 exomes

AF:

0.738

AC:

185431

AN:

251262

Hom.:

69573

AF XY:

0.744

AC XY:

101094

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.846

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.770

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.783

Gnomad FIN exome

AF:

0.756

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.764

AC:

1114762

AN:

1459750

Hom.:

427923

Cov.:

AF XY:

0.764

AC XY:

555177

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.851

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.771

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.775

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.773

Gnomad4 OTH exome

AF:

0.759

GnomAD4 genome

AF:

0.775

AC:

117926

AN:

152088

Hom.:

46068

Cov.:

AF XY:

0.771

AC XY:

57318

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.844

Gnomad4 AMR

AF:

0.701

Gnomad4 ASJ

AF:

0.772

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.780

Gnomad4 FIN

AF:

0.748

Gnomad4 NFE

AF:

0.774

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.767

Hom.:

114403

Bravo

AF:

0.773

TwinsUK

AF:

0.770

AC:

2856

ALSPAC

AF:

0.766

AC:

2953

ESP6500AA

AF:

0.828

AC:

3648

ESP6500EA

AF:

0.770

AC:

6620

ExAC

AF:

0.747

AC:

90657

Asia WGS

AF:

0.662

AC:

2304

AN:

3478

EpiCase

AF:

0.773

EpiControl

AF:

0.773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.017

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0000026

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

3.1

REVEL

Benign

0.12

Sift

Benign

0.23

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.094

MPC

0.42

ClinPred

0.023

GERP RS

5.0

Varity_R

0.039

gMVP

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over