9-112268089-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001163788.4(PTBP3):ā€‹c.311A>Gā€‹(p.Asn104Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3868774).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTBP3NM_001163788.4 linkuse as main transcriptc.311A>G p.Asn104Ser missense_variant 4/14 ENST00000374257.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTBP3ENST00000374257.6 linkuse as main transcriptc.311A>G p.Asn104Ser missense_variant 4/142 NM_001163788.4 P1O95758-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
251012
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135670
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461282
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
726966
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 10, 2024The c.404A>G (p.N135S) alteration is located in exon 1 (coding exon 1) of the PTBP3 gene. This alteration results from a A to G substitution at nucleotide position 404, causing the asparagine (N) at amino acid position 135 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
0.12
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
.;.;.;T;.;T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D;D;D;D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.39
T;T;T;T;T;T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
1.3
.;.;.;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.7
D;D;D;D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0050
D;D;D;D;D;D
Sift4G
Uncertain
0.014
D;D;D;D;D;.
Polyphen
0.13
B;B;.;B;.;.
Vest4
0.36
MutPred
0.61
.;.;.;Gain of disorder (P = 0.0727);.;.;
MVP
0.48
MPC
0.16
ClinPred
0.71
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.41

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.

Other links and lift over

dbSNP: rs757764387; hg19: chr9-115030369; COSMIC: COSV52958061; COSMIC: COSV52958061; API