rs10420407

Variant names:

• chr19-803945-G-A
• rs10420407
• NM_002819.5:c.116-91G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001411140.1(PTBP1):​c.122-91G>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_001411140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411140.1. 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
	PTBP1	NM_002819.5	MANE Select	c.116-91G>A		intron	N/A	NP_002810.1
	PTBP1	NM_001411140.1		c.122-91G>A		intron	N/A	NP_001398069.1
	PTBP1	NM_031990.4		c.116-91G>A		intron	N/A	NP_114367.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.116-91G>A		intron	N/A	ENSP00000349428.4
	PTBP1	ENST00000394601.8	TSL:1	c.116-91G>A		intron	N/A	ENSP00000408096.1
	PTBP1	ENST00000349038.8	TSL:1	c.116-91G>A		intron	N/A	ENSP00000014112.5

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

African (AFR) AF: 0.0663 AC: 2023 AN: 30516

American (AMR) AF: 0.162 AC: 6781 AN: 41808

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3229 AN: 23990

East Asian (EAS) AF: 0.0369 AC: 1442 AN: 39122

South Asian (SAS) AF: 0.120 AC: 9637 AN: 80470

European-Finnish (FIN) AF: 0.0498 AC: 2251 AN: 45196

Middle Eastern (MID) AF: 0.164 AC: 826 AN: 5046

European-Non Finnish (NFE) AF: 0.0872 AC: 88969 AN: 1020118

Other (OTH) AF: 0.0978 AC: 5515 AN: 56396

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

African (AFR) AF: 0.0644 AC: 2673 AN: 41498

American (AMR) AF: 0.152 AC: 2327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3472

East Asian (EAS) AF: 0.0429 AC: 222 AN: 5172

South Asian (SAS) AF: 0.120 AC: 577 AN: 4822

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0899 AC: 6110 AN: 67982

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0902 Hom.: 208

Bravo AF: 0.0941

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.31
PhyloP100		-0.54
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10420407; hg19: chr19-803945;