Variant rs3918392 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.532A>G(p.Thr178Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,613,380 control chromosomes in the GnomAD database, including 1,589 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.051 ( 237 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1352 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.386

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=0.002142042).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.532A>G	p.Thr178Ala	missense_variant	6/22	ENST00000356518.7	NP_079496.1	Q9BZ11-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAM33	ENST00000356518.7 link	c.532A>G	p.Thr178Ala	missense_variant	6/22	1	NM_025220.5	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8 link	c.532A>G	p.Thr178Ala	missense_variant	6/22	1		ENSP00000369190.4	A2A2L3
ADAM33	ENST00000350009.6 link	c.532A>G	p.Thr178Ala	missense_variant	6/21	5		ENSP00000322550.5	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.0505

AC:

7673

AN:

152068

Hom.:

237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0780

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.0479

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0447

AC:

11090

AN:

248154

Hom.:

338

AF XY:

0.0442

AC XY:

5935

AN XY:

134126

show subpopulations

Gnomad AFR exome

AF:

0.0799

Gnomad AMR exome

AF:

0.0332

Gnomad ASJ exome

AF:

0.0548

Gnomad EAS exome

AF:

0.0901

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0254

Gnomad NFE exome

AF:

0.0369

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0402

AC:

58772

AN:

1461194

Hom.:

1352

Cov.:

AF XY:

0.0405

AC XY:

29473

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.0764

Gnomad4 AMR exome

AF:

0.0343

Gnomad4 ASJ exome

AF:

0.0502

Gnomad4 EAS exome

AF:

0.0923

Gnomad4 SAS exome

AF:

0.0504

Gnomad4 FIN exome

AF:

0.0273

Gnomad4 NFE exome

AF:

0.0368

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0506

AC:

7694

AN:

152186

Hom.:

237

Cov.:

AF XY:

0.0505

AC XY:

3759

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0783

Gnomad4 AMR

AF:

0.0497

Gnomad4 ASJ

AF:

0.0479

Gnomad4 EAS

AF:

0.0839

Gnomad4 SAS

AF:

0.0517

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0592

Alfa

AF:

0.0402

Hom.:

148

Bravo

AF:

0.0532

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0374

AC:

144

ESP6500AA

AF:

0.0788

AC:

347

ESP6500EA

AF:

0.0344

AC:

296

ExAC

AF:

0.0454

AC:

5514

Asia WGS

AF:

0.0770

AC:

265

AN:

3478

EpiCase

AF:

0.0361

EpiControl

AF:

0.0383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.60

DANN

Benign

0.70

DEOGEN2

Benign

0.071

T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.018

T;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.63

N;N;.;N

REVEL

Benign

0.034

Sift

Benign

0.67

T;T;.;T

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.016

MPC

0.17

ClinPred

0.000016

GERP RS

2.0

Varity_R

0.022

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over