Variant 20-3671144-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025220.5(ADAM33):c.2102C>A(p.Thr701Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,612,756 control chromosomes in the GnomAD database, including 3 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 0.0024 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00037 ( 2 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005074948).

BP6

Variant 20-3671144-G-T is Benign according to our data. Variant chr20-3671144-G-T is described in ClinVar as [Benign]. Clinvar id is 784404.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.2102C>A	p.Thr701Asn	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.2102C>A	p.Thr701Asn	missense_variant	19/22	1	NM_025220.5	ENSP00000348912	P4	Q9BZ11-1
ADAM33	ENST00000379861.8 linkuse as main transcript	c.2102C>A	p.Thr701Asn	missense_variant	19/22	1		ENSP00000369190	A2
ADAM33	ENST00000466620.5 linkuse as main transcript	n.1663C>A		non_coding_transcript_exon_variant	8/11	1
ADAM33	ENST00000350009.6 linkuse as main transcript	c.2024C>A	p.Thr675Asn	missense_variant	18/21	5		ENSP00000322550	A2	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00692

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.000813

AC:

201

AN:

247184

Hom.:

AF XY:

0.000619

AC XY:

AN XY:

134054

show subpopulations

Gnomad AFR exome

AF:

0.00739

Gnomad AMR exome

AF:

0.00134

Gnomad ASJ exome

AF:

0.00131

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000366

AC:

534

AN:

1460404

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

245

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.00714

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152352

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00695

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000711

Hom.:

Bravo

AF:

0.00294

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000906

AC:

110

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.079

T;.;T;.

Eigen

Benign

0.026

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.73

T;T;T;T

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

L;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;.;N

REVEL

Benign

0.15

Sift

Benign

0.15

T;T;.;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.83

P;P;.;P

Vest4

0.15

MVP

0.47

MPC

0.18

ClinPred

0.020

GERP RS

4.7

Varity_R

0.11

gMVP

0.74

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over