NM_002819.5:c.264C>T

Variant names:

• chr19-804184-C-T
• rs61757784
• NM_002819.5:c.264C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002819.5(PTBP1):​c.264C>T​(p.Leu88Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,609,044 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (14 hom.)
• Consequence: PTBP1 NM_002819.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0420
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 19-804184-C-T is Benign according to our data. Variant chr19-804184-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 788832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.
• BS2: High AC in GnomAd4 at 512 AD gene.

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.264C>T	p.Leu88Leu	synonymous	Exon 4 of 15	NP_002810.1	P26599-3
	PTBP1	NM_001411140.1		c.270C>T	p.Leu90Leu	synonymous	Exon 4 of 15	NP_001398069.1	A0A7I2V621
	PTBP1	NM_031990.4		c.264C>T	p.Leu88Leu	synonymous	Exon 4 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.264C>T	p.Leu88Leu	synonymous	Exon 4 of 15	ENSP00000349428.4	P26599-3
	PTBP1	ENST00000394601.8	TSL:1	c.264C>T	p.Leu88Leu	synonymous	Exon 4 of 15	ENSP00000408096.1	P26599-2
	PTBP1	ENST00000349038.8	TSL:1	c.264C>T	p.Leu88Leu	synonymous	Exon 4 of 14	ENSP00000014112.5	P26599-1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 512 AN: 152170 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00326 AC: 810 AN: 248326 AF XY: 0.00308

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.00739

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000932

Gnomad NFE exome AF: 0.00415

Gnomad OTH exome AF: 0.00531

GnomAD4 exome AF: 0.00409 AC: 5960 AN: 1456756 Hom.: 14 Cov.: 33 AF XY: 0.00401 AC XY: 2900 AN XY: 723964

African (AFR) AF: 0.000901 AC: 30 AN: 33306

American (AMR) AF: 0.00761 AC: 337 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 87 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.000651 AC: 56 AN: 86034

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53280

Middle Eastern (MID) AF: 0.000873 AC: 5 AN: 5726

European-Non Finnish (NFE) AF: 0.00467 AC: 5175 AN: 1108584

Other (OTH) AF: 0.00428 AC: 257 AN: 60110

GnomAD4 genome AF: 0.00336 AC: 512 AN: 152288 Hom.: 4 Cov.: 33 AF XY: 0.00344 AC XY: 256 AN XY: 74470

African (AFR) AF: 0.00106 AC: 44 AN: 41560

American (AMR) AF: 0.00941 AC: 144 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00426 AC: 290 AN: 68002

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00368 Hom.: 2

Bravo AF: 0.00349

EpiCase AF: 0.00453

EpiControl AF: 0.00463

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.7
DANN	Benign	0.90
PhyloP100		0.042
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs61757784; hg19: chr19-804184; COSMIC: COSV100609302; COSMIC: COSV100609302;