19-804613-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002819.5(PTBP1):c.517G>A(p.Ala173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,612,492 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

PTBP1
NM_002819.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.54

Publications

2 publications found

Variant links:

Genes affected

PTBP1 (HGNC:9583): (polypyrimidine tract binding protein 1) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has four repeats of quasi-RNA recognition motif (RRM) domains that bind RNAs. This protein binds to the intronic polypyrimidine tracts that requires pre-mRNA splicing and acts via the protein degradation ubiquitin-proteasome pathway. It may also promote the binding of U2 snRNP to pre-mRNAs. This protein is localized in the nucleoplasm and it is also detected in the perinucleolar structure. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PTBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008741975).

BP6

Variant 19-804613-G-A is Benign according to our data. Variant chr19-804613-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 721042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 202 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002819.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP1	NM_002819.5	MANE Select	c.517G>A	p.Ala173Thr	missense	Exon 6 of 15	NP_002810.1	P26599-3
PTBP1	NM_001411140.1		c.523G>A	p.Ala175Thr	missense	Exon 6 of 15	NP_001398069.1	A0A7I2V621
PTBP1	NM_031990.4		c.517G>A	p.Ala173Thr	missense	Exon 6 of 15	NP_114367.1	P26599-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.517G>A	p.Ala173Thr	missense	Exon 6 of 15	ENSP00000349428.4	P26599-3
PTBP1	ENST00000394601.8	TSL:1	c.517G>A	p.Ala173Thr	missense	Exon 6 of 15	ENSP00000408096.1	P26599-2
PTBP1	ENST00000349038.8	TSL:1	c.517G>A	p.Ala173Thr	missense	Exon 6 of 14	ENSP00000014112.5	P26599-1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00144

AC:

356

AN:

247870

AF XY:

0.00141

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000993

Gnomad FIN exome

AF:

0.000752

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00134

AC:

1959

AN:

1460122

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

995

AN XY:

726426

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33464

American (AMR)

AF:

0.00159

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26108

East Asian (EAS)

AF:

0.000529

AC:

AN:

39686

South Asian (SAS)

AF:

0.00372

AC:

321

AN:

86232

European-Finnish (FIN)

AF:

0.000672

AC:

AN:

52084

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00124

AC:

1381

AN:

1111730

Other (OTH)

AF:

0.00161

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

116

232

349

465

581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00133

AC:

202

AN:

152370

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41594

American (AMR)

AF:

0.00281

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5178

South Asian (SAS)

AF:

0.00352

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00141

AC:

AN:

68034

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000889

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00140

AC:

170

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00190

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.016

MetaRNN

Benign

0.0087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

3.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.38

REVEL

Benign

0.071

Sift

Benign

0.61

Sift4G

Benign

0.41

Polyphen

0.0050

Vest4

0.39

MVP

0.65

MPC

0.45

ClinPred

0.0080

GERP RS

4.8

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.084

gMVP

0.37

Mutation Taster

=99/1

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

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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