22-19196276-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_007098.4(CLTCL1):c.4181T>C(p.Ile1394Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0655 in 1,613,068 control chromosomes in the GnomAD database, including 3,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.059 ( 330 hom., cov: 33)
Exomes 𝑓: 0.066 ( 3364 hom. )
Consequence
CLTCL1
NM_007098.4 missense
NM_007098.4 missense
Scores
1
2
11
Clinical Significance
Conservation
PhyloP100: 4.61
Genes affected
CLTCL1 (HGNC:2093): (clathrin heavy chain like 1) This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0033106506).
BP6
?
Variant 22-19196276-A-G is Benign according to our data. Variant chr22-19196276-A-G is described in ClinVar as [Benign]. Clinvar id is 3059365.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLTCL1 | NM_007098.4 | c.4181T>C | p.Ile1394Thr | missense_variant | 26/33 | ENST00000427926.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLTCL1 | ENST00000427926.6 | c.4181T>C | p.Ile1394Thr | missense_variant | 26/33 | 1 | NM_007098.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0589 AC: 8957AN: 152088Hom.: 330 Cov.: 33
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GnomAD3 exomes AF: 0.0654 AC: 16226AN: 248290Hom.: 559 AF XY: 0.0635 AC XY: 8558AN XY: 134758
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GnomAD4 exome AF: 0.0662 AC: 96728AN: 1460862Hom.: 3364 Cov.: 31 AF XY: 0.0655 AC XY: 47586AN XY: 726748
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GnomAD4 genome ? AF: 0.0589 AC: 8967AN: 152206Hom.: 330 Cov.: 33 AF XY: 0.0584 AC XY: 4346AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CLTCL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 27, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
Sift4G
Benign
T;T;D;T
Polyphen
B;B;.;.
Vest4
ClinPred
T
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