9-112223964-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163788.4(PTBP3):​c.1462C>T​(p.Leu488Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.12
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTBP3NM_001163788.4 linkuse as main transcriptc.1462C>T p.Leu488Phe missense_variant 14/14 ENST00000374257.6 NP_001157260.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTBP3ENST00000374257.6 linkuse as main transcriptc.1462C>T p.Leu488Phe missense_variant 14/142 NM_001163788.4 ENSP00000363375 P1O95758-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249358
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000589
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:
0.00000137
AC:
2
AN:
1459606
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725936
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000452
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
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 GeneticsOct 06, 2021The c.1555C>T (p.L519F) alteration is located in exon 1 (coding exon 1) of the PTBP3 gene. This alteration results from a C to T substitution at nucleotide position 1555, causing the leucine (L) at amino acid position 519 to be replaced by a phenylalanine (F). 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.035
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;.;T;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.72
D;D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.1
.;.;.;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.9
D;D;D;D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
1.0
D;D;.;D;.
Vest4
0.69
MutPred
0.63
.;.;.;Gain of MoRF binding (P = 0.1421);.;
MVP
0.60
MPC
2.1
ClinPred
0.93
D
GERP RS
5.8
Varity_R
0.52
gMVP
0.79

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: rs771735559; hg19: chr9-114986244; API