Variant 20-3671118-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025220.5(ADAM33):c.2128G>A(p.Val710Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,606,170 control chromosomes in the GnomAD database, including 6,687 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 Uncertain significance (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.067 ( 449 hom., cov: 34)

Exomes 𝑓: 0.088 ( 6238 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.27

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]

ADAM33 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016098917).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.2128G>A	p.Val710Ile	missense_variant	19/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7 linkuse as main transcript	c.2128G>A	p.Val710Ile	missense_variant	19/22	1	NM_025220.5	ENSP00000348912	P4	Q9BZ11-1
ADAM33	ENST00000379861.8 linkuse as main transcript	c.2128G>A	p.Val710Ile	missense_variant	19/22	1		ENSP00000369190	A2
ADAM33	ENST00000466620.5 linkuse as main transcript	n.1689G>A		non_coding_transcript_exon_variant	8/11	1
ADAM33	ENST00000350009.6 linkuse as main transcript	c.2050G>A	p.Val684Ile	missense_variant	18/21	5		ENSP00000322550	A2	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

10158

AN:

152158

Hom.:

449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0510

Gnomad ASJ

AF:

0.0668

Gnomad EAS

AF:

0.0181

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.0603

GnomAD3 exomes

AF:

0.0763

AC:

17939

AN:

235174

Hom.:

901

AF XY:

0.0807

AC XY:

10305

AN XY:

127644

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.0325

Gnomad ASJ exome

AF:

0.0705

Gnomad EAS exome

AF:

0.0179

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.0876

Gnomad OTH exome

AF:

0.0781

GnomAD4 exome

AF:

0.0880

AC:

127887

AN:

1453894

Hom.:

6238

Cov.:

AF XY:

0.0887

AC XY:

64090

AN XY:

722660

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.0337

Gnomad4 ASJ exome

AF:

0.0699

Gnomad4 EAS exome

AF:

0.0107

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0919

Gnomad4 OTH exome

AF:

0.0821

GnomAD4 genome

AF:

0.0667

AC:

10161

AN:

152276

Hom.:

449

Cov.:

AF XY:

0.0693

AC XY:

5162

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0510

Gnomad4 ASJ

AF:

0.0668

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.0905

Gnomad4 OTH

AF:

0.0597

Alfa

AF:

0.0800

Hom.:

724

Bravo

AF:

0.0568

TwinsUK

AF:

0.0930

AC:

345

ALSPAC

AF:

0.0906

AC:

349

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.0881

AC:

757

ExAC

AF:

0.0743

AC:

9009

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.041

T;.;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.64

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

N;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.47

N;N;.;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.069

B;B;.;B

Vest4

0.044

MPC

0.048

ClinPred

0.0016

GERP RS

3.5

Varity_R

0.029

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over