1-52414811-C-T

Variant summary

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

The NM_032864.4(PRPF38A):​c.799C>T​(p.Arg267Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PRPF38A
NM_032864.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94
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]
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]

Genome browser will be placed here

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=0.40083528).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRPF38ANM_032864.4 linkuse as main transcriptc.799C>T p.Arg267Cys missense_variant 8/10 ENST00000257181.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRPF38AENST00000257181.10 linkuse as main transcriptc.799C>T p.Arg267Cys missense_variant 8/101 NM_032864.4 P1Q8NAV1-1
PRPF38AENST00000474048.1 linkuse as main transcriptn.587C>T non_coding_transcript_exon_variant 6/81
TUT4ENST00000528457.5 linkuse as main transcriptc.375-6351G>A intron_variant 3
TUT4ENST00000527941.5 linkuse as main transcriptc.*68-5205G>A intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250980
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461888
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000216
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMay 31, 2023The c.799C>T (p.R267C) alteration is located in exon 8 (coding exon 8) of the PRPF38A gene. This alteration results from a C to T substitution at nucleotide position 799, causing the arginine (R) at amino acid position 267 to be replaced by a cysteine (C). 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
0.95
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.60
MutPred
0.26
Gain of catalytic residue at R267 (P = 0.0608);
MVP
0.33
MPC
0.59
ClinPred
0.95
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56
gMVP
0.47

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.

Other links and lift over

dbSNP: rs758321944; hg19: chr1-52880483; API