rs771875399

Variant names:

• chr9-112250991-C-A
• NM_001163788.4:c.740G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-112250991-C-A
• chr9-112250991-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001163788.4(PTBP3):​c.740G>T​(p.Arg247Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,459,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R247H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP3	NM_001163788.4	c.740G>T	p.Arg247Leu	missense_variant	Exon 7 of 14	ENST00000374257.6	NP_001157260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP3	ENST00000374257.6	c.740G>T	p.Arg247Leu	missense_variant	Exon 7 of 14	2	NM_001163788.4	ENSP00000363375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1459934 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;.;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	.;.;.;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.9	D;D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		0.10	B;B;.;P;.
Vest4		0.82
MutPred		0.49		.;.;.;Loss of disorder (P = 0.0358);.;
MVP		0.46
MPC		0.26
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-115013271; COSMIC: COSV100533935; COSMIC: COSV100533935;