2-152671338-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001365597.4(PRPF40A):c.1540A>G(p.Ile514Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000152 in 1,574,096 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PRPF40A
NM_001365597.4 missense
NM_001365597.4 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 4.98
Genes affected
PRPF40A (HGNC:16463): (pre-mRNA processing factor 40 homolog A) Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08893201).
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF40A | NM_001365597.4 | c.1540A>G | p.Ile514Val | missense_variant | 14/26 | ENST00000545856.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF40A | ENST00000545856.8 | c.1540A>G | p.Ile514Val | missense_variant | 14/26 | 1 | NM_001365597.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000324 AC: 7AN: 215796Hom.: 0 AF XY: 0.0000509 AC XY: 6AN XY: 117834
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GnomAD4 exome AF: 0.0000134 AC: 19AN: 1421910Hom.: 0 Cov.: 29 AF XY: 0.0000198 AC XY: 14AN XY: 706384
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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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 | Mar 13, 2023 | The c.1414A>G (p.I472V) alteration is located in exon 14 (coding exon 14) of the PRPF40A gene. This alteration results from a A to G substitution at nucleotide position 1414, causing the isoleucine (I) at amino acid position 472 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
REVEL
Benign
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at