Genetic Variant PTBP1:p.Asn108Asn (chr19-804327-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002819.5(PTBP1):c.324C>T(p.Asn108Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,613,602 control chromosomes in the GnomAD database, including 7,142 homozygotes. 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 0.091 ( 751 hom., cov: 33)

Exomes 𝑓: 0.090 ( 6391 hom. )

Consequence

PTBP1
NM_002819.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=2.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5 link	c.324C>T	p.Asn108Asn	synonymous_variant	Exon 5 of 15	ENST00000356948.11	NP_002810.1	P26599-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11 link	c.324C>T	p.Asn108Asn	synonymous_variant	Exon 5 of 15	1	NM_002819.5	ENSP00000349428.4		P26599-3

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

13911

AN:

152192

Hom.:

749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0429

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0519

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0981

AC:

24501

AN:

249720

Hom.:

1392

AF XY:

0.0989

AC XY:

13366

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.0813

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.0391

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.0497

Gnomad NFE exome

AF:

0.0891

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.0899

AC:

131402

AN:

1461292

Hom.:

6391

Cov.:

AF XY:

0.0913

AC XY:

66361

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0829

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.0369

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.0493

Gnomad4 NFE exome

AF:

0.0868

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.0914

AC:

13922

AN:

152310

Hom.:

751

Cov.:

AF XY:

0.0919

AC XY:

6848

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0806

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0519

Gnomad4 NFE

AF:

0.0900

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0880

Hom.:

278

Bravo

AF:

0.0995

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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