Variant 20-3671034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025220.5(ADAM33):c.2212G>A(p.Gly738Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,403,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADAM33
NM_025220.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.979

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071799725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.2212G>A	p.Gly738Ser	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.2212G>A	p.Gly738Ser	missense_variant	19/22	1	NM_025220.5	ENSP00000348912	P4	Q9BZ11-1
ADAM33	ENST00000379861.8 linkuse as main transcript	c.2212G>A	p.Gly738Ser	missense_variant	19/22	1		ENSP00000369190	A2
ADAM33	ENST00000466620.5 linkuse as main transcript	n.1773G>A		non_coding_transcript_exon_variant	8/11	1
ADAM33	ENST00000350009.6 linkuse as main transcript	c.2134G>A	p.Gly712Ser	missense_variant	18/21	5		ENSP00000322550	A2	Q9BZ11-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1403780

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

693212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.2212G>A (p.G738S) alteration is located in exon 19 (coding exon 19) of the ADAM33 gene. This alteration results from a G to A substitution at nucleotide position 2212, causing the glycine (G) at amino acid position 738 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.9

DANN

Benign

0.96

DEOGEN2

Benign

0.090

T;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.072

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

M;.;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

N;N;.;N

REVEL

Benign

0.021

Sift

Benign

0.41

T;T;.;T

Sift4G

Benign

0.83

T;T;T;T

Polyphen

0.062

B;B;.;B

Vest4

0.12

MutPred

0.21

Gain of phosphorylation at G738 (P = 0.0723);Gain of phosphorylation at G738 (P = 0.0723);.;.;

MVP

0.15

MPC

0.069

ClinPred

0.089

GERP RS

2.6

Varity_R

0.037

gMVP

0.43

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