12-122272933-T-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001247997.2(CLIP1):c.4259A>T(p.Glu1420Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,100 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: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
CLIP1
NM_001247997.2 missense
NM_001247997.2 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 5.79
Genes affected
CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CLIP1. . Trascript score misZ 3.4483 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, intellectual disability.
BP4
Computational evidence support a benign effect (MetaRNN=0.35684696).
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLIP1 | NM_001247997.2 | c.4259A>T | p.Glu1420Val | missense_variant | 26/26 | ENST00000620786.5 | NP_001234926.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLIP1 | ENST00000620786.5 | c.4259A>T | p.Glu1420Val | missense_variant | 26/26 | 5 | NM_001247997.2 | ENSP00000479322 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251490Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135920
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727248
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
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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 | Jan 16, 2024 | The c.4226A>T (p.E1409V) alteration is located in exon 25 (coding exon 24) of the CLIP1 gene. This alteration results from a A to T substitution at nucleotide position 4226, causing the glutamic acid (E) at amino acid position 1409 to be replaced by a valine (V). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;.;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D;D;D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;.;.;.;L;.;.;L
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N;N;.;N;.;N
REVEL
Uncertain
Sift
Uncertain
.;.;D;D;.;D;.;D
Sift4G
Uncertain
D;.;D;D;D;D;.;D
Polyphen
0.81, 0.41
.;.;P;P;B;P;.;B
Vest4
MutPred
0.45
.;.;.;.;Loss of disorder (P = 0.0028);.;.;Loss of disorder (P = 0.0028);
MVP
MPC
1.1
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