rs12590471

Variant names:

• chr14-70534383-G-A
• rs12590471
• NM_003814.5:c.-177+414C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003814.5(ADAM20):​c.-177+414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,698 control chromosomes in the GnomAD database, including 6,980 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 0.26 (6980 hom., cov: 31)
• Consequence: ADAM20 NM_003814.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 4 publications found

Genes affected

ADAM20 (HGNC:199): (ADAM metallopeptidase domain 20) 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. The expression of this gene is testis-specific. [provided by RefSeq, Jul 2008]

ADAM20 Gene-Disease associations (from GenCC):

• male infertility

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000257759 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM20	NM_003814.5	c.-177+414C>T		intron_variant	Intron 1 of 1	ENST00000256389.5	NP_003805.4
ADAM20	XM_005268151.4	c.-26-9450C>T		intron_variant	Intron 1 of 1		XP_005268208.1
LOC105370556	XR_007064239.1	n.69-3002G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM20	ENST00000256389.5	c.-177+414C>T		intron_variant	Intron 1 of 1	1	NM_003814.5	ENSP00000256389.3
ADAM20	ENST00000652041.1	c.-27+414C>T		intron_variant	Intron 1 of 1			ENSP00000498512.1
ENSG00000257759	ENST00000556646.1	n.183+12899C>T		intron_variant	Intron 1 of 2	4
ENSG00000293824	ENST00000719268.1	n.289-18562C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39416 AN: 151580 Hom.: 6954 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39496 AN: 151698 Hom.: 6980 Cov.: 31 AF XY: 0.260 AC XY: 19235 AN XY: 74086

African (AFR) AF: 0.471 AC: 19479 AN: 41360

American (AMR) AF: 0.185 AC: 2819 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2896 AN: 5160

South Asian (SAS) AF: 0.253 AC: 1213 AN: 4800

European-Finnish (FIN) AF: 0.0985 AC: 1032 AN: 10478

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10564 AN: 67904

Other (OTH) AF: 0.265 AC: 555 AN: 2094

Alfa AF: 0.198 Hom.: 2152

Bravo AF: 0.279

Asia WGS AF: 0.444 AC: 1543 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12590471; hg19: chr14-71001100;