20-3668784-A-G

Variant names:

• chr20-3668784-A-G
• rs677044
• NM_025220.5:c.*179T>C

Variant summary

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

The NM_025220.5(ADAM33):​c.*179T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 712,174 control chromosomes in the GnomAD database, including 17,916 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 0.24 (4780 hom., cov: 32)
  • Exomes 𝑓: 0.21 (13136 hom.)
• Consequence: ADAM33 NM_025220.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*179T>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518	c.*179T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36783 AN: 151822 Hom.: 4773 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.211 AC: 118401 AN: 560234 Hom.: 13136 Cov.: 6 AF XY: 0.210 AC XY: 63208 AN XY: 301034

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.242 AC: 36806 AN: 151940 Hom.: 4780 Cov.: 32 AF XY: 0.241 AC XY: 17900 AN XY: 74250

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.238

Alfa AF: 0.210 Hom.: 3228

Bravo AF: 0.253

Asia WGS AF: 0.211 AC: 736 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	2.2
DANN	Benign	0.48

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: rs677044; hg19: chr20-3649431; COSMIC: COSV62933840;