chr12-49637760-T-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.1703T>A(p.Phe568Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,611,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
PRPF40B
NM_001031698.3 missense
NM_001031698.3 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 7.93
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 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF40B | NM_001031698.3 | c.1703T>A | p.Phe568Tyr | missense_variant | 18/26 | ENST00000548825.7 | NP_001026868.2 | |
FMNL3 | NM_175736.5 | c.*8055A>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.1703T>A | p.Phe568Tyr | missense_variant | 18/26 | 5 | NM_001031698.3 | ENSP00000448073 | P3 | |
FMNL3 | ENST00000335154.10 | c.*8055A>T | 3_prime_UTR_variant | 26/26 | 1 | NM_175736.5 | ENSP00000335655 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151940Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250852Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135632
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459882Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 726390
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151940Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74204
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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 | Dec 11, 2023 | The c.1637T>A (p.F546Y) alteration is located in exon 17 (coding exon 17) of the PRPF40B gene. This alteration results from a T to A substitution at nucleotide position 1637, causing the phenylalanine (F) at amino acid position 546 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;.;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0, 1.0
.;D;D
Vest4
MutPred
0.54
.;.;Gain of catalytic residue at L541 (P = 0.0055);
MVP
MPC
ClinPred
D
GERP RS
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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