Genetic Variant NM_001163788.4:c.1475G>C (chr9-112223951-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001163788.4(PTBP3):c.1475G>C(p.Gly492Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G492E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

Publications

0 publications found

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]

PTBP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17590562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP3	NM_001163788.4	MANE Select	c.1475G>C	p.Gly492Ala	missense	Exon 14 of 14	NP_001157260.1	O95758-6
PTBP3	NM_001244898.1		c.1577G>C	p.Gly526Ala	missense	Exon 14 of 14	NP_001231827.1	O95758-4
PTBP3	NM_001163790.2		c.1568G>C	p.Gly523Ala	missense	Exon 15 of 15	NP_001157262.1	O95758-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTBP3	ENST00000374257.6	TSL:2 MANE Select	c.1475G>C	p.Gly492Ala	missense	Exon 14 of 14	ENSP00000363375.1	O95758-6
PTBP3	ENST00000210227.5	TSL:2	c.1577G>C	p.Gly526Ala	missense	Exon 14 of 14	ENSP00000210227.5
PTBP3	ENST00000450374.2	TSL:5	c.1568G>C	p.Gly523Ala	missense	Exon 15 of 15	ENSP00000388024.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461044

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111576

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.051

Eigen

Benign

-0.24

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Benign

0.017

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

PhyloP100

2.8

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.3

REVEL

Benign

0.14

Sift

Benign

0.31

Sift4G

Benign

0.62

Polyphen

0.0060

Vest4

0.15

MutPred

0.40

Gain of helix (P = 0.132)

MVP

0.28

MPC

0.98

ClinPred

0.26

GERP RS

5.9

Varity_R

0.13

gMVP

0.71

Mutation Taster

=76/24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over