1-52411180-A-C

Variant summary

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

The NM_032864.4(PRPF38A):ā€‹c.478A>Cā€‹(p.Ile160Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,010 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

PRPF38A
NM_032864.4 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
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=0.2847797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRPF38ANM_032864.4 linkuse as main transcriptc.478A>C p.Ile160Leu missense_variant 4/10 ENST00000257181.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRPF38AENST00000257181.10 linkuse as main transcriptc.478A>C p.Ile160Leu missense_variant 4/101 NM_032864.4 P1Q8NAV1-1
PRPF38AENST00000474048.1 linkuse as main transcriptn.287-1334A>C intron_variant, non_coding_transcript_variant 1
TUT4ENST00000528457.5 linkuse as main transcriptc.375-2720T>G intron_variant 3
TUT4ENST00000527941.5 linkuse as main transcriptc.*68-1574T>G intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251130
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
3
AN:
1460822
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
726822
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

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 GeneticsFeb 28, 2023The c.478A>C (p.I160L) alteration is located in exon 4 (coding exon 4) of the PRPF38A gene. This alteration results from a A to C substitution at nucleotide position 478, causing the isoleucine (I) at amino acid position 160 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
0.64
BayesDel_addAF
Uncertain
0.041
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.099
T
Eigen
Benign
0.091
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.42
Sift
Benign
0.031
D
Sift4G
Benign
0.19
T
Polyphen
0.23
B
Vest4
0.42
MutPred
0.71
Gain of loop (P = 0.1069);
MVP
0.52
MPC
1.0
ClinPred
0.69
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.49
gMVP
0.49

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: rs774012364; hg19: chr1-52876852; API