chr12-49642299-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001031698.3(PRPF40B):c.1949G>A(p.Arg650His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 1 hom. )
Consequence
PRPF40B
NM_001031698.3 missense
NM_001031698.3 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 9.31
Genes affected
PRPF40B (HGNC:25031): (pre-mRNA processing factor 40 homolog B) This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants. [provided by RefSeq, Aug 2014]
FMNL3 (HGNC:23698): (formin like 3) The protein encoded by this gene contains a formin homology 2 domain and has high sequence identity to the mouse Wbp3 protein. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF40B | NM_001031698.3 | c.1949G>A | p.Arg650His | missense_variant | 20/26 | ENST00000548825.7 | NP_001026868.2 | |
FMNL3 | NM_175736.5 | c.*3516C>T | 3_prime_UTR_variant | 26/26 | ENST00000335154.10 | NP_783863.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRPF40B | ENST00000548825.7 | c.1949G>A | p.Arg650His | missense_variant | 20/26 | 5 | NM_001031698.3 | ENSP00000448073 | P3 | |
FMNL3 | ENST00000335154.10 | c.*3516C>T | 3_prime_UTR_variant | 26/26 | 1 | NM_175736.5 | ENSP00000335655 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249622Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135050
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461826Hom.: 1 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727196
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74374
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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 | Aug 26, 2022 | The c.1883G>A (p.R628H) alteration is located in exon 19 (coding exon 19) of the PRPF40B gene. This alteration results from a G to A substitution at nucleotide position 1883, causing the arginine (R) at amino acid position 628 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.39
.;.;Gain of catalytic residue at M626 (P = 0.0175);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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