chr8-144395327-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_013291.3(CPSF1):c.3125C>T(p.Thr1042Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,613,484 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
CPSF1
NM_013291.3 missense
NM_013291.3 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 4.49
Genes affected
CPSF1 (HGNC:2324): (cleavage and polyadenylation specific factor 1) Cleavage and polyadenylation specificity factor (CPSF) is a multisubunit complex that plays a central role in 3-prime processing of pre-mRNAs. CPSF recognizes the AAUAAA signal in the pre-mRNA and interacts with other proteins to facilitate both RNA cleavage and poly(A) synthesis. CPSF1 is the largest subunit of the CPSF complex (Murthy and Manley, 1995 [PubMed 7590244]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.036494583).
BS2
High AC in GnomAdExome4 at 73 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPSF1 | NM_013291.3 | c.3125C>T | p.Thr1042Met | missense_variant | 28/38 | ENST00000616140.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPSF1 | ENST00000616140.2 | c.3125C>T | p.Thr1042Met | missense_variant | 28/38 | 1 | NM_013291.3 | P1 | |
CPSF1 | ENST00000620219.4 | c.3125C>T | p.Thr1042Met | missense_variant | 27/37 | 1 | P1 | ||
CPSF1 | ENST00000529288.1 | n.574C>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
CPSF1 | ENST00000531042.5 | c.388-304C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152092Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000920 AC: 23AN: 250096Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135514
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GnomAD4 exome AF: 0.0000500 AC: 73AN: 1461274Hom.: 0 Cov.: 44 AF XY: 0.0000399 AC XY: 29AN XY: 726938
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74420
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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 22, 2023 | The c.3125C>T (p.T1042M) alteration is located in exon 28 (coding exon 27) of the CPSF1 gene. This alteration results from a C to T substitution at nucleotide position 3125, causing the threonine (T) at amino acid position 1042 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MVP
ClinPred
T
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