1-52413939-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032864.4(PRPF38A):​c.670C>T​(p.Arg224Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R224G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PRPF38A
NM_032864.4 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRPF38ANM_032864.4 linkc.670C>T p.Arg224Cys missense_variant Exon 6 of 10 ENST00000257181.10 NP_116253.2 Q8NAV1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRPF38AENST00000257181.10 linkc.670C>T p.Arg224Cys missense_variant Exon 6 of 10 1 NM_032864.4 ENSP00000257181.8 Q8NAV1-1
PRPF38AENST00000474048.1 linkn.458C>T non_coding_transcript_exon_variant Exon 4 of 8 1
TUT4ENST00000528457.5 linkc.374-5479G>A intron_variant Intron 2 of 2 3 ENSP00000432475.1 H0YCX5
TUT4ENST00000527941.5 linkn.*68-4333G>A intron_variant Intron 3 of 4 5 ENSP00000436810.1 H0YEY0

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251364
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461830
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152254
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000818
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.20
Sift
Benign
0.091
T
Sift4G
Uncertain
0.0030
D
Polyphen
0.99
D
Vest4
0.69
MutPred
0.33
Gain of catalytic residue at P223 (P = 0.0157);
MVP
0.23
MPC
0.59
ClinPred
0.67
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.51

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: rs142879021; hg19: chr1-52879611; COSMIC: COSV57122368; COSMIC: COSV57122368; API