chr19-804311-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002819.5(PTBP1):​c.308C>T​(p.Thr103Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PTBP1
NM_002819.5 missense

Scores

13
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTBP1NM_002819.5 linkc.308C>T p.Thr103Met missense_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
PTBP1ENST00000356948.11 linkc.308C>T p.Thr103Met missense_variant Exon 5 of 15 1 NM_002819.5 ENSP00000349428.4 P26599-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249776
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135208
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461432
Hom.:
0
Cov.:
33
AF XY:
0.00000688
AC XY:
5
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.308C>T (p.T103M) alteration is located in exon 5 (coding exon 5) of the PTBP1 gene. This alteration results from a C to T substitution at nucleotide position 308, causing the threonine (T) at amino acid position 103 to be replaced by a methionine (M). 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
0.22
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
.;.;D;.;.;T;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.45
T;T;T;T;T;T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.0
M;.;M;.;M;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;.;D;.;D;.;D
REVEL
Benign
0.17
Sift
Uncertain
0.019
D;.;D;.;D;.;T
Sift4G
Benign
0.065
T;T;T;D;T;T;T
Polyphen
0.99, 1.0
.;.;D;.;D;.;.
Vest4
0.65
MutPred
0.31
Loss of disorder (P = 0.1074);Loss of disorder (P = 0.1074);Loss of disorder (P = 0.1074);.;Loss of disorder (P = 0.1074);Loss of disorder (P = 0.1074);.;
MVP
0.76
MPC
0.61
ClinPred
0.91
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.55

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.

Other links and lift over

dbSNP: rs1452968841; hg19: chr19-804311; API