Variant chr11-60899214-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014502.5(PRPF19):c.919A>G(p.Ser307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRPF19
NM_014502.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Variant links:

Genes affected

PRPF19 (HGNC:17896): (pre-mRNA processing factor 19) Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; cellular protein metabolic process; and mRNA splicing, via spliceosome. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear speck; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome. Colocalizes with DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

PRPF19 links:

PRPF19 (HGNC:):

PRPF19 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07298243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF19	NM_014502.5 linkuse as main transcript	c.919A>G	p.Ser307Gly	missense_variant	11/16	ENST00000227524.9	NP_055317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRPF19	ENST00000227524.9 linkuse as main transcript	c.919A>G	p.Ser307Gly	missense_variant	11/16	1	NM_014502.5	ENSP00000227524.4	Q9UMS4
PRPF19	ENST00000541371.5 linkuse as main transcript	c.719-636A>G		intron_variant		3		ENSP00000440266.1	F5GY56
PRPF19	ENST00000540473.5 linkuse as main transcript	c.114+2096A>G		intron_variant		5		ENSP00000443031.1	H0YGF3
PRPF19	ENST00000539960.1 linkuse as main transcript	n.2A>G		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251252

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.919A>G (p.S307G) alteration is located in exon 11 (coding exon 11) of the PRPF19 gene. This alteration results from a A to G substitution at nucleotide position 919, causing the serine (S) at amino acid position 307 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.087

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.86

M_CAP

Benign

0.0098

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-1.4

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.95

REVEL

Benign

0.22

Sift

Benign

0.72

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.068

MVP

0.39

MPC

1.0

ClinPred

0.14

GERP RS

5.9

Varity_R

0.13

gMVP

0.16

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over