20-3671718-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_025220.5(ADAM33):c.1768A>G(p.Met590Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,586,898 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0054 ( 5 hom., cov: 34)
Exomes 𝑓: 0.00086 ( 7 hom. )
Consequence
ADAM33
NM_025220.5 missense
NM_025220.5 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -0.298
Genes affected
ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]
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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=0.0029089153).
BP6
?
Variant 20-3671718-T-C is Benign according to our data. Variant chr20-3671718-T-C is described in ClinVar as [Benign]. Clinvar id is 769071.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00538 (819/152310) while in subpopulation AFR AF= 0.0179 (745/41588). AF 95% confidence interval is 0.0168. There are 5 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM33 | NM_025220.5 | c.1768A>G | p.Met590Val | missense_variant | 16/22 | ENST00000356518.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM33 | ENST00000356518.7 | c.1768A>G | p.Met590Val | missense_variant | 16/22 | 1 | NM_025220.5 | P4 | |
ADAM33 | ENST00000379861.8 | c.1768A>G | p.Met590Val | missense_variant | 16/22 | 1 | A2 | ||
ADAM33 | ENST00000466620.5 | n.1407A>G | non_coding_transcript_exon_variant | 6/11 | 1 | ||||
ADAM33 | ENST00000350009.6 | c.1768A>G | p.Met590Val | missense_variant | 16/21 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00539 AC: 820AN: 152192Hom.: 5 Cov.: 34
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GnomAD3 exomes AF: 0.00175 AC: 360AN: 206076Hom.: 4 AF XY: 0.00133 AC XY: 148AN XY: 110894
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GnomAD4 exome AF: 0.000862 AC: 1237AN: 1434588Hom.: 7 Cov.: 35 AF XY: 0.000770 AC XY: 548AN XY: 711262
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GnomAD4 genome ? AF: 0.00538 AC: 819AN: 152310Hom.: 5 Cov.: 34 AF XY: 0.00486 AC XY: 362AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;B
Vest4
MVP
MPC
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