chr9-112275953-A-C

Variant names:

• chr9-112275953-A-C
• NM_001163788.4:c.95T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001163788.4(PTBP3):​c.95T>G​(p.Val32Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V32I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

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.95T>G	p.Val32Gly	missense	Exon 3 of 14	NP_001157260.1	O95758-6
	PTBP3	NM_001244898.1		c.197T>G	p.Val66Gly	missense	Exon 3 of 14	NP_001231827.1	O95758-4
	PTBP3	NM_001163790.2		c.188T>G	p.Val63Gly	missense	Exon 4 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.95T>G	p.Val32Gly	missense	Exon 3 of 14	ENSP00000363375.1	O95758-6
	PTBP3	ENST00000210227.5	TSL:2	c.197T>G	p.Val66Gly	missense	Exon 3 of 14	ENSP00000210227.5
	PTBP3	ENST00000450374.2	TSL:5	c.188T>G	p.Val63Gly	missense	Exon 4 of 15	ENSP00000388024.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.62		Loss of stability (P = 0.0039)
MVP		0.91
MPC		0.63
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.79
Mutation Taster		=21/79	disease causing

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

hg19: chr9-115038233;