rs10420407

Positions:

• chr19-803945-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002819.5(PTBP1):​c.116-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,494,826 control chromosomes in the GnomAD database, including 6,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.087 (695 hom., cov: 33)
  • Exomes 𝑓: 0.090 (5867 hom.)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

Genes affected

PTBP1 (HGNC:9583): (polypyrimidine tract binding protein 1) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA-binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has four repeats of quasi-RNA recognition motif (RRM) domains that bind RNAs. This protein binds to the intronic polypyrimidine tracts that requires pre-mRNA splicing and acts via the protein degradation ubiquitin-proteasome pathway. It may also promote the binding of U2 snRNP to pre-mRNAs. This protein is localized in the nucleoplasm and it is also detected in the perinucleolar structure. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PTBP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.116-91G>A		intron_variant		ENST00000356948.11	NP_002810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.116-91G>A		intron_variant		1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13189 AN: 152046 Hom.: 694 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0899 AC: 120673 AN: 1342662 Hom.: 5867 AF XY: 0.0911 AC XY: 61253 AN XY: 672044

Gnomad4 AFR exome AF: 0.0663

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.0369

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0872

Gnomad4 OTH exome AF: 0.0978

GnomAD4 genome AF: 0.0867 AC: 13196 AN: 152164 Hom.: 695 Cov.: 33 AF XY: 0.0874 AC XY: 6506 AN XY: 74408

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0429

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0829 Hom.: 74

Bravo AF: 0.0941

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10420407; hg19: chr19-803945;