Genetic Variant PTBP3:p.Met263Val (chr9-112250944-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001163788.4(PTBP3):c.787A>G(p.Met263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,599,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Publications

4 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06115532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP3	NM_001163788.4	MANE Select	c.787A>G	p.Met263Val	missense	Exon 7 of 14	NP_001157260.1	O95758-6
PTBP3	NM_001244898.1		c.889A>G	p.Met297Val	missense	Exon 7 of 14	NP_001231827.1	O95758-4
PTBP3	NM_001163790.2		c.880A>G	p.Met294Val	missense	Exon 8 of 15	NP_001157262.1	O95758-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP3	ENST00000374257.6	TSL:2 MANE Select	c.787A>G	p.Met263Val	missense	Exon 7 of 14	ENSP00000363375.1	O95758-6
PTBP3	ENST00000210227.5	TSL:2	c.889A>G	p.Met297Val	missense	Exon 7 of 14	ENSP00000210227.5
PTBP3	ENST00000450374.2	TSL:5	c.880A>G	p.Met294Val	missense	Exon 8 of 15	ENSP00000388024.2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000142

AC:

AN:

239736

AF XY:

0.000116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

228

AN:

1447674

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

116

AN XY:

720068

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32494

American (AMR)

AF:

0.000378

AC:

AN:

42374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25514

East Asian (EAS)

AF:

0.00

AC:

AN:

39094

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83724

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000183

AC:

202

AN:

1105796

Other (OTH)

AF:

0.0000836

AC:

AN:

59826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000289

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

41396

American (AMR)

AF:

0.00190

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.022

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.011

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

M_CAP

Benign

0.0097

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

1.7

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.079

Sift

Benign

0.14

Sift4G

Benign

0.65

Polyphen

0.0080

Vest4

0.17

MVP

0.35

MPC

0.12

ClinPred

0.053

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.43

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over