Genetic Variant PTBP3:p.Thr335Ser (chr9-112232116-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001163788.4(PTBP3):c.1003A>T(p.Thr335Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000558 in 1,611,896 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

Variant links:

Genes affected

PTBP3 (HGNC:10253): (polypyrimidine tract binding protein 3) The protein encoded by this gene binds RNA and is a regulator of cell differentiation. The encoded protein preferentially binds to poly(G) and poly(U) sequences in vitro. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PTBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044759065).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP3	NM_001163788.4 link	c.1003A>T	p.Thr335Ser	missense_variant	Exon 9 of 14	ENST00000374257.6	NP_001157260.1	O95758-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP3	ENST00000374257.6 link	c.1003A>T	p.Thr335Ser	missense_variant	Exon 9 of 14	2	NM_001163788.4	ENSP00000363375.1		O95758-6

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.000721

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000361

AC:

AN:

249512

Hom.:

AF XY:

0.000378

AC XY:

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000733

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000576

AC:

841

AN:

1459872

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

413

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000713

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000388

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000721

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000576

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1096A>T (p.T366S) alteration is located in exon 1 (coding exon 1) of the PTBP3 gene. This alteration results from a A to T substitution at nucleotide position 1096, causing the threonine (T) at amino acid position 366 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.16

DEOGEN2

Benign

0.029

.;.;.;T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

T;T;T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.045

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

.;.;.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

2.2

N;N;N;N;N

REVEL

Benign

0.073

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;.;B;.

Vest4

0.13

MVP

0.19

MPC

0.11

ClinPred

0.037

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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