20-3668493-T-C

Position:

• chr20-3668493-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025220.5(ADAM33):​c.*470A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 178,758 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (396 hom., cov: 32)
  • Exomes 𝑓: 0.025 (21 hom.)
• Consequence: ADAM33 NM_025220.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*470A>G		3_prime_UTR_variant	22/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518	c.*470A>G		3_prime_UTR_variant	22/22	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9630 AN: 152018 Hom.: 393 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0692

GnomAD4 exome AF: 0.0254 AC: 675 AN: 26622 Hom.: 21 Cov.: 0 AF XY: 0.0260 AC XY: 362 AN XY: 13948

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.0446

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.0535

Gnomad4 SAS exome AF: 0.0263

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0634 AC: 9642 AN: 152136 Hom.: 396 Cov.: 32 AF XY: 0.0653 AC XY: 4857 AN XY: 74386

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0776

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0427 Hom.: 165

Bravo AF: 0.0689

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs3746631; hg19: chr20-3649140;