rs8103323

Variant names:

• chr19-798921-T-C
• rs8103323
• NM_002819.5:c.9-492T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-798921-T-C
• chr19-798921-T-G

Variant summary

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

The NM_002819.5(PTBP1):​c.9-492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,142 control chromosomes in the GnomAD database, including 8,341 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 0.32 (8341 hom., cov: 33)
• Consequence: PTBP1 NM_002819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTBP1	NM_002819.5	c.9-492T>C		intron_variant	Intron 1 of 14	ENST00000356948.11	NP_002810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTBP1	ENST00000356948.11	c.9-492T>C		intron_variant	Intron 1 of 14	1	NM_002819.5	ENSP00000349428.4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49080 AN: 152024 Hom.: 8319 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49143 AN: 152142 Hom.: 8341 Cov.: 33 AF XY: 0.330 AC XY: 24583 AN XY: 74390

African (AFR) AF: 0.330 AC: 13708 AN: 41504

American (AMR) AF: 0.432 AC: 6604 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.0666 AC: 345 AN: 5184

South Asian (SAS) AF: 0.412 AC: 1992 AN: 4832

European-Finnish (FIN) AF: 0.365 AC: 3866 AN: 10586

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20707 AN: 67950

Other (OTH) AF: 0.324 AC: 684 AN: 2114

Alfa AF: 0.316 Hom.: 6282

Bravo AF: 0.322

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-4.0
PromoterAI		0.024	Neutral
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: rs8103323; hg19: chr19-798921;