chr12-49636808-C-T
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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.1519C>T(p.Arg507Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
PRPF40B
NM_001031698.3 missense
NM_001031698.3 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 2.24
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 GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF40B | NM_001031698.3 | c.1519C>T | p.Arg507Trp | missense_variant | 16/26 | ENST00000548825.7 | NP_001026868.2 | |
FMNL3 | NM_175736.5 | c.*9007G>A | 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.1519C>T | p.Arg507Trp | missense_variant | 16/26 | 5 | NM_001031698.3 | ENSP00000448073 | P3 | |
PRPF40B | ENST00000380281.6 | c.1519C>T | p.Arg507Trp | missense_variant | 16/26 | 1 | ENSP00000369634 | A2 | ||
PRPF40B | ENST00000261897.5 | c.1435C>T | p.Arg479Trp | missense_variant | 15/25 | 1 | ENSP00000261897 | |||
FMNL3 | ENST00000335154.10 | c.*9007G>A | 3_prime_UTR_variant | 26/26 | 1 | NM_175736.5 | ENSP00000335655 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251480Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135914
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GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50AN XY: 727234
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74350
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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 | Sep 30, 2021 | The c.1453C>T (p.R485W) alteration is located in exon 15 (coding exon 15) of the PRPF40B gene. This alteration results from a C to T substitution at nucleotide position 1453, causing the arginine (R) at amino acid position 485 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
.;D;D
REVEL
Benign
Sift
Pathogenic
.;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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