NM_002819.5:c.517G>C

Variant names:

• chr19-804613-G-C
• rs150661031
• NM_002819.5:c.517G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002819.5(PTBP1):​c.517G>C​(p.Ala173Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A173T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PTBP1 NM_002819.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28873035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002819.5. 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.517G>C	p.Ala173Pro	missense	Exon 6 of 15	NP_002810.1	P26599-3
	PTBP1	NM_001411140.1		c.523G>C	p.Ala175Pro	missense	Exon 6 of 15	NP_001398069.1	A0A7I2V621
	PTBP1	NM_031990.4		c.517G>C	p.Ala173Pro	missense	Exon 6 of 15	NP_114367.1	P26599-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTBP1	ENST00000356948.11	TSL:1 MANE Select	c.517G>C	p.Ala173Pro	missense	Exon 6 of 15	ENSP00000349428.4	P26599-3
	PTBP1	ENST00000394601.8	TSL:1	c.517G>C	p.Ala173Pro	missense	Exon 6 of 15	ENSP00000408096.1	P26599-2
	PTBP1	ENST00000349038.8	TSL:1	c.517G>C	p.Ala173Pro	missense	Exon 6 of 14	ENSP00000014112.5	P26599-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0079	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N
PhyloP100		3.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.15	T
Polyphen		0.65	P
Vest4		0.34
MutPred		0.45		Gain of glycosylation at A173 (P = 0.0578)
MVP		0.56
MPC		0.61
ClinPred		0.44	T
GERP RS		4.8
PromoterAI		-0.041	Neutral
Varity_R		0.49
gMVP		0.56
Mutation Taster		=74/26	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

Other links and lift over

dbSNP: rs150661031; hg19: chr19-804613;