NM_001163788.4:c.403G>C

Variant names:

• chr9-112262548-C-G
• rs369648690
• NM_001163788.4:c.403G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163788.4(PTBP3):​c.403G>C​(p.Ala135Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A135T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 0 publications found

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

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=0.1093936).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP3	NM_001163788.4	MANE Select	c.403G>C	p.Ala135Pro	missense	Exon 5 of 14	NP_001157260.1	O95758-6
	PTBP3	NM_001244898.1		c.505G>C	p.Ala169Pro	missense	Exon 5 of 14	NP_001231827.1	O95758-4
	PTBP3	NM_001163790.2		c.496G>C	p.Ala166Pro	missense	Exon 6 of 15	NP_001157262.1	O95758-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP3	ENST00000374257.6	TSL:2 MANE Select	c.403G>C	p.Ala135Pro	missense	Exon 5 of 14	ENSP00000363375.1	O95758-6
	PTBP3	ENST00000210227.5	TSL:2	c.505G>C	p.Ala169Pro	missense	Exon 5 of 14	ENSP00000210227.5
	PTBP3	ENST00000450374.2	TSL:5	c.496G>C	p.Ala166Pro	missense	Exon 6 of 15	ENSP00000388024.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.62	N
PhyloP100		0.55
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.016
Sift	Benign	0.38	T
Sift4G	Benign	0.30	T
Polyphen		0.10	B
Vest4		0.24
MutPred		0.30		Gain of glycosylation at A163 (P = 0.0141)
MVP		0.51
MPC		0.17
ClinPred		0.14	T
GERP RS		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.55
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs369648690; hg19: chr9-115024828;