Genetic Variant PTTG1IP:p.Gly8Arg (chr21-44873595-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004339.4(PTTG1IP):c.22G>C(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,452,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PTTG1IP
NM_004339.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24138653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTTG1IP	NM_004339.4 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 6	ENST00000330938.8	NP_004330.1	P53801
PTTG1IP	NM_001286822.2 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 3		NP_001273751.1	P53801B4DPZ0
PTTG1IP	NR_104597.2 link	n.96G>C		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTTG1IP	ENST00000330938.8 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 6	1	NM_004339.4	ENSP00000328325.3	P53801
PTTG1IP	ENST00000445724.3 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 3	2		ENSP00000395374.2	B4DPZ0
PTTG1IP	ENST00000397887.7 link	c.22G>C	p.Gly8Arg	missense_variant	Exon 1 of 4	4		ENSP00000380984.3	A8MZH8
PTTG1IP	ENST00000480234.1 link	n.74G>C		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1300778

Hom.:

Cov.:

AF XY:

0.00000936

AC XY:

AN XY:

641086

show subpopulations

Gnomad4 AFR exome

AF:

0.000344

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.69

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.7

N;N;D

REVEL

Benign

0.091

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.39

MutPred

0.37

Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);Gain of MoRF binding (P = 0.0142);

MVP

0.36

MPC

1.0

ClinPred

0.87

GERP RS

1.8

Varity_R

0.068

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over