Variant chr21-44861255-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004339.4(PTTG1IP):c.185C>G(p.Thr62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,613,530 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 36 hom. )

Consequence

PTTG1IP
NM_004339.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

PTTG1IP (HGNC:13524): (PTTG1 interacting protein) This gene encodes a single-pass type I integral membrane protein, which binds to pituitary tumor-transforming 1 protein (PTTG1), and facilitates translocation of PTTG1 into the nucleus. Coexpression of this protein and PTTG1 induces transcriptional activation of basic fibroblast growth factor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

PTTG1IP 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=0.004667282).

BP6

Variant 21-44861255-G-C is Benign according to our data. Variant chr21-44861255-G-C is described in ClinVar as [Benign]. Clinvar id is 719550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTTG1IP	NM_004339.4 link	c.185C>G	p.Thr62Ser	missense_variant	Exon 3 of 6	ENST00000330938.8	NP_004330.1	P53801
PTTG1IP	NM_001286822.2 link	c.168+4140C>G		intron_variant	Intron 2 of 2		NP_001273751.1	P53801B4DPZ0
PTTG1IP	NR_104597.2 link	n.242+4140C>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTTG1IP	ENST00000330938.8 link	c.185C>G	p.Thr62Ser	missense_variant	Exon 3 of 6	1	NM_004339.4	ENSP00000328325.3		P53801

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00553

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00516

AC:

1294

AN:

250938

Hom.:

AF XY:

0.00498

AC XY:

676

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00448

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000426

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.00659

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00557

AC:

8136

AN:

1461180

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

3890

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00605

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.00602

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.00419

AC:

639

AN:

152350

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.00553

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.00326

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00509

AC:

618

EpiCase

AF:

0.00545

EpiControl

AF:

0.00450

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 02, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.010

.;B;.

Vest4

0.25

MutPred

0.19

Gain of ubiquitination at K64 (P = 0.0931);Gain of ubiquitination at K64 (P = 0.0931);.;

MVP

0.45

MPC

0.25

ClinPred

0.0097

GERP RS

3.2

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.036

gMVP

0.25

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