rs12479696

Positions:

• chr20-3669310-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025220.5(ADAM33):​c.2393C>T​(p.Pro798Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM33 NM_025220.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060658753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5	c.2393C>T	p.Pro798Leu	missense_variant	21/22	ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.2393C>T	p.Pro798Leu	missense_variant	21/22	1	NM_025220.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444126 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 718162

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.15	T;.;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.061	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.020	N;N;.;N
REVEL	Benign	0.017
Sift	Benign	0.18	T;T;.;T
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.053	B;B;P;B
Vest4		0.065
MutPred		0.14		Loss of phosphorylation at S797 (P = 0.1628);Loss of phosphorylation at S797 (P = 0.1628);.;.;
MVP		0.37
MPC		0.057
ClinPred		0.088	T
GERP RS		3.2
Varity_R		0.061
gMVP		0.14

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

Other links and lift over

dbSNP: rs12479696; hg19: chr20-3649957;