9-112262526-T-C

Variant names:

• chr9-112262526-T-C
• rs771097183
• NM_001163788.4:c.425A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001163788.4(PTBP3):​c.425A>G​(p.Asn142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,611,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: PTBP3 NM_001163788.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023290306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP3	NM_001163788.4	c.425A>G	p.Asn142Ser	missense_variant	Exon 5 of 14	ENST00000374257.6	NP_001157260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP3	ENST00000374257.6	c.425A>G	p.Asn142Ser	missense_variant	Exon 5 of 14	2	NM_001163788.4	ENSP00000363375.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000765 AC: 19 AN: 248352 AF XY: 0.0000819

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1459530 Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42 AN XY: 726072

Gnomad4 AFR exome AF: 0.0000900 AC: 3 AN: 33338

Gnomad4 AMR exome AF: 0.0000678 AC: 3 AN: 44268

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26110

Gnomad4 EAS exome AF: 0.000278 AC: 11 AN: 39524

Gnomad4 SAS exome AF: 0.000199 AC: 17 AN: 85628

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53390

Gnomad4 NFE exome AF: 0.0000297 AC: 33 AN: 1111212

Gnomad4 Remaining exome AF: 0.0000663 AC: 4 AN: 60302

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74386

Gnomad4 AFR AF: 0.0000482 AC: 0.0000482323 AN: 0.0000482323

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206782 AN: 0.000206782

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000824 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518A>G (p.N173S) alteration is located in exon 1 (coding exon 1) of the PTBP3 gene. This alteration results from a A to G substitution at nucleotide position 518, causing the asparagine (N) at amino acid position 173 to be replaced by a serine (S). 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	Benign	0.047
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.5
DANN	Benign	0.67
DEOGEN2	Benign	0.016	.;.;.;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.77	T;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.023	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.38	.;.;.;N;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.17	N;N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.63	T;T;T;T;T;T
Sift4G	Benign	0.83	T;T;T;T;T;.
Polyphen		0.0	B;B;.;B;.;.
Vest4		0.075
MutPred		0.24		.;.;.;Gain of phosphorylation at N170 (P = 0.0353);.;.;
MVP		0.16
MPC		0.096
ClinPred		0.0051	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.17
Mutation Taster		=94/6	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

Publications

LitVar

Other links and lift over

dbSNP: rs771097183; hg19: chr9-115024806;