chr9-112231403-G-A

Position:

• chr9-112231403-G-A

Variant summary

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

The NM_001163788.4(PTBP3):​c.1031C>T​(p.Pro344Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

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]

ACMG classification

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
PTBP3	NM_001163788.4	c.1031C>T	p.Pro344Leu	missense_variant	10/14	ENST00000374257.6	NP_001157260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP3	ENST00000374257.6	c.1031C>T	p.Pro344Leu	missense_variant	10/14	2	NM_001163788.4	ENSP00000363375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

The c.1124C>T (p.P375L) 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 1124, causing the proline (P) at amino acid position 375 to be replaced by a leucine (L). 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	0.93
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;.;.;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.81	.;.;.;L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-9.8	D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.99	D;D;.;D;.
Vest4		0.57
MutPred		0.57		.;.;.;Gain of helix (P = 0.2294);.;
MVP		0.62
MPC		1.0
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114993683;