8-144395469-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_013291.3(CPSF1):c.3062C>T(p.Thr1021Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,612,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
CPSF1
NM_013291.3 missense
NM_013291.3 missense
Scores
8
4
3
Clinical Significance
Conservation
PhyloP100: 5.06
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPSF1 | NM_013291.3 | c.3062C>T | p.Thr1021Met | missense_variant | 27/38 | ENST00000616140.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPSF1 | ENST00000616140.2 | c.3062C>T | p.Thr1021Met | missense_variant | 27/38 | 1 | NM_013291.3 | P1 | |
CPSF1 | ENST00000620219.4 | c.3062C>T | p.Thr1021Met | missense_variant | 26/37 | 1 | P1 | ||
CPSF1 | ENST00000529288.1 | n.511C>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
CPSF1 | ENST00000531042.5 | c.388-446C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152126Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250150Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135588
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460802Hom.: 0 Cov.: 44 AF XY: 0.0000261 AC XY: 19AN XY: 726710
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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 | May 25, 2022 | The c.3062C>T (p.T1021M) alteration is located in exon 27 (coding exon 26) of the CPSF1 gene. This alteration results from a C to T substitution at nucleotide position 3062, causing the threonine (T) at amino acid position 1021 to be replaced by a methionine (M). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at T1021 (P = 0.0651);Loss of catalytic residue at T1021 (P = 0.0651);
MVP
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