19-804327-C-T

Variant names:

• chr19-804327-C-T
• rs10420953
• NM_002819.5:c.324C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000356948.11(PTBP1):​c.324C>T​(p.Asn108Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,613,602 control chromosomes in the GnomAD database, including 7,142 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 0.091 (751 hom., cov: 33)
  • Exomes 𝑓: 0.090 (6391 hom.)
• Consequence: PTBP1 ENST00000356948.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=2.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356948.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	NM_002819.5	MANE Select	c.324C>T	p.Asn108Asn	synonymous	Exon 5 of 15	NP_002810.1
	PTBP1	NM_001411140.1		c.330C>T	p.Asn110Asn	synonymous	Exon 5 of 15	NP_001398069.1
	PTBP1	NM_031990.4		c.324C>T	p.Asn108Asn	synonymous	Exon 5 of 15	NP_114367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.324C>T	p.Asn108Asn	synonymous	Exon 5 of 15	ENSP00000349428.4
	PTBP1	ENST00000394601.8	TSL:1	c.324C>T	p.Asn108Asn	synonymous	Exon 5 of 15	ENSP00000408096.1
	PTBP1	ENST00000349038.8	TSL:1	c.324C>T	p.Asn108Asn	synonymous	Exon 5 of 14	ENSP00000014112.5

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13911 AN: 152192 Hom.: 749 Cov.: 33

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0981 AC: 24501 AN: 249720 AF XY: 0.0989

Gnomad AFR exome AF: 0.0813

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.0391

Gnomad FIN exome AF: 0.0497

Gnomad NFE exome AF: 0.0891

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.0899 AC: 131402 AN: 1461292 Hom.: 6391 Cov.: 35 AF XY: 0.0913 AC XY: 66361 AN XY: 726936

African (AFR) AF: 0.0829 AC: 2774 AN: 33476

American (AMR) AF: 0.163 AC: 7289 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3495 AN: 26124

East Asian (EAS) AF: 0.0369 AC: 1464 AN: 39694

South Asian (SAS) AF: 0.120 AC: 10362 AN: 86242

European-Finnish (FIN) AF: 0.0493 AC: 2616 AN: 53084

Middle Eastern (MID) AF: 0.162 AC: 929 AN: 5738

European-Non Finnish (NFE) AF: 0.0868 AC: 96498 AN: 1111898

Other (OTH) AF: 0.0990 AC: 5975 AN: 60384

GnomAD4 genome AF: 0.0914 AC: 13922 AN: 152310 Hom.: 751 Cov.: 33 AF XY: 0.0919 AC XY: 6848 AN XY: 74476

African (AFR) AF: 0.0806 AC: 3352 AN: 41572

American (AMR) AF: 0.154 AC: 2355 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5188

South Asian (SAS) AF: 0.120 AC: 579 AN: 4830

European-Finnish (FIN) AF: 0.0519 AC: 552 AN: 10630

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0900 AC: 6118 AN: 68010

Other (OTH) AF: 0.103 AC: 219 AN: 2116

Alfa AF: 0.0880 Hom.: 278

Bravo AF: 0.0995

Asia WGS AF: 0.0980 AC: 340 AN: 3478

EpiCase AF: 0.100

EpiControl AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		2.8
PromoterAI		-0.082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs10420953; hg19: chr19-804327; COSMIC: COSV62459966; COSMIC: COSV62459966;