9-112262583-A-T

Variant names:

• chr9-112262583-A-T
• rs760356684
• NM_001163788.4:c.368T>A

Variant summary

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

The NM_001163788.4(PTBP3):​c.368T>A​(p.Leu123Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,450,054 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L123P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.368T>A	p.Leu123Gln	missense	Exon 5 of 14	NP_001157260.1	O95758-6
	PTBP3	NM_001244898.1		c.470T>A	p.Leu157Gln	missense	Exon 5 of 14	NP_001231827.1	O95758-4
	PTBP3	NM_001163790.2		c.461T>A	p.Leu154Gln	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.368T>A	p.Leu123Gln	missense	Exon 5 of 14	ENSP00000363375.1	O95758-6
	PTBP3	ENST00000210227.5	TSL:2	c.470T>A	p.Leu157Gln	missense	Exon 5 of 14	ENSP00000210227.5
	PTBP3	ENST00000450374.2	TSL:5	c.461T>A	p.Leu154Gln	missense	Exon 6 of 15	ENSP00000388024.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000421 AC: 1 AN: 237430 AF XY: 0.00000778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1450054 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720998

African (AFR) AF: 0.00 AC: 0 AN: 32834

American (AMR) AF: 0.00 AC: 0 AN: 41936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.00 AC: 0 AN: 39042

South Asian (SAS) AF: 0.00 AC: 0 AN: 83824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107664

Other (OTH) AF: 0.00 AC: 0 AN: 59918

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.37
Sift	Benign	0.094	T
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.44		Gain of solvent accessibility (P = 0.0137)
MVP		0.81
MPC		0.58
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.43
gMVP		0.78
Mutation Taster		=72/28	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: rs760356684; hg19: chr9-115024863;