NM_021794.4:c.2309A>G

Variant names:

• chr1-119894028-T-C
• NM_021794.4:c.2309A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021794.4(ADAM30):​c.2309A>G​(p.Glu770Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM30 NM_021794.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.25
• Publications: 0 publications found

Genes affected

ADAM30 (HGNC:208): (ADAM metallopeptidase domain 30) 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 gene is testis-specific and contains a polymorphic region, resulting in isoforms with varying numbers of C-terminal repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032947958).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021794.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM30	NM_021794.4	MANE Select	c.2309A>G	p.Glu770Gly	missense	Exon 1 of 1	NP_068566.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM30	ENST00000369400.2	TSL:6 MANE Select	c.2309A>G	p.Glu770Gly	missense	Exon 1 of 1	ENSP00000358407.1	Q9UKF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.56
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-5.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.020
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.075
MutPred		0.11		Gain of MoRF binding (P = 0.0234)
MVP		0.061
MPC		0.12
ClinPred		0.10	T
GERP RS		-0.70
Varity_R		0.024
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

hg19: chr1-120436651;