14-70523428-C-G

Position:

• chr14-70523428-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003814.5(ADAM20):​c.1330G>C​(p.Gly444Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ADAM20 NM_003814.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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]

ENSG00000257759 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM20	NM_003814.5	c.1330G>C	p.Gly444Arg	missense_variant	2/2	ENST00000256389.5	NP_003805.4
ADAM20	XM_005268151.4	c.1480G>C	p.Gly494Arg	missense_variant	2/2		XP_005268208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM20	ENST00000256389.5	c.1330G>C	p.Gly444Arg	missense_variant	2/2	1	NM_003814.5	ENSP00000256389.3
ADAM20	ENST00000652041.1	c.1480G>C	p.Gly494Arg	missense_variant	2/2			ENSP00000498512.1
ENSG00000257759	ENST00000556646.1	n.183+23854G>C		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461796 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.1480G>C (p.G494R) alteration is located in exon 2 (coding exon 1) of the ADAM20 gene. This alteration results from a G to C substitution at nucleotide position 1480, causing the glycine (G) at amino acid position 494 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.055
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.17
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.023	D
Vest4		0.43
MVP		0.50
MPC		0.22
ClinPred		0.99	D
GERP RS		4.5

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-70990145;