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GeneBe

20-3669598-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_025220.5(ADAM33):c.2280C>T(p.Gly760=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,603,656 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00037 ( 4 hom. )

Consequence

ADAM33
NM_025220.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41
Variant links:
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-3669598-G-A is Benign according to our data. Variant chr20-3669598-G-A is described in ClinVar as [Benign]. Clinvar id is 769070.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.41 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAM33NM_025220.5 linkuse as main transcriptc.2280C>T p.Gly760= synonymous_variant 20/22 ENST00000356518.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAM33ENST00000356518.7 linkuse as main transcriptc.2280C>T p.Gly760= synonymous_variant 20/221 NM_025220.5 P4Q9BZ11-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00359
AC:
546
AN:
151910
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00113
AC:
259
AN:
229132
Hom.:
3
AF XY:
0.000760
AC XY:
94
AN XY:
123634
show subpopulations
Gnomad AFR exome
AF:
0.0145
Gnomad AMR exome
AF:
0.00123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000581
Gnomad SAS exome
AF:
0.0000363
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000579
Gnomad OTH exome
AF:
0.000718
GnomAD4 exome
AF:
0.000371
AC:
538
AN:
1451628
Hom.:
4
Cov.:
32
AF XY:
0.000333
AC XY:
240
AN XY:
720824
show subpopulations
Gnomad4 AFR exome
AF:
0.0116
Gnomad4 AMR exome
AF:
0.00139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000102
Gnomad4 SAS exome
AF:
0.0000239
Gnomad4 FIN exome
AF:
0.0000762
Gnomad4 NFE exome
AF:
0.0000280
Gnomad4 OTH exome
AF:
0.000767
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00358
AC:
545
AN:
152028
Hom.:
3
Cov.:
33
AF XY:
0.00318
AC XY:
236
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0123
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00195
Hom.:
0
Bravo
AF:
0.00440

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.32
Dann
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145743069; hg19: chr20-3650245; API