Variant 1-52414845-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032864.4(PRPF38A):c.833G>T(p.Arg278Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PRPF38A
NM_032864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

PRPF38A (HGNC:25930): (pre-mRNA processing factor 38A) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

PRPF38A links:

PRPF38A (HGNC:):

PRPF38A links:

TUT4 (HGNC:28981): (terminal uridylyl transferase 4) Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; negative regulation of transposition, RNA-mediated; and stem cell population maintenance. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleolus. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

TUT4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42021555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF38A	NM_032864.4 linkuse as main transcript	c.833G>T	p.Arg278Leu	missense_variant	8/10	ENST00000257181.10	NP_116253.2	Q8NAV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRPF38A	ENST00000257181.10 linkuse as main transcript	c.833G>T	p.Arg278Leu	missense_variant	8/10	1	NM_032864.4	ENSP00000257181.8	Q8NAV1-1
PRPF38A	ENST00000474048.1 linkuse as main transcript	n.621G>T		non_coding_transcript_exon_variant	6/8	1
TUT4	ENST00000528457.5 linkuse as main transcript	c.374-6385C>A		intron_variant		3		ENSP00000432475.1	H0YCX5
TUT4	ENST00000527941.5 linkuse as main transcript	n.*68-5239C>A		intron_variant		5		ENSP00000436810.1	H0YEY0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250042

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000324

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.833G>T (p.R278L) alteration is located in exon 8 (coding exon 8) of the PRPF38A gene. This alteration results from a G to T substitution at nucleotide position 833, causing the arginine (R) at amino acid position 278 to be replaced by a leucine (L). 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

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Benign

0.038

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.051

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.43

Sift

Benign

0.083

Sift4G

Uncertain

0.016

Polyphen

0.18

Vest4

0.66

MutPred

0.24

Loss of methylation at R278 (P = 0.0419);

MVP

0.67

MPC

0.54

ClinPred

0.70

GERP RS

5.7

Varity_R

0.19

gMVP

0.46

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