NM_021794.4:c.2079G>C

Variant names:

• chr1-119894258-C-G
• rs748073569
• NM_021794.4:c.2079G>C

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.2079G>C​(p.Met693Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM30 NM_021794.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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=0.0477179).

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.2079G>C	p.Met693Ile	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.2079G>C	p.Met693Ile	missense	Exon 1 of 1	ENSP00000358407.1	Q9UKF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.011
DANN	Benign	0.63
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.0060
Sift	Benign	0.33	T
Sift4G	Benign	0.45	T
Polyphen		0.0020	B
Vest4		0.042
MutPred		0.47		Gain of sheet (P = 0.0266)
MVP		0.12
MPC		0.11
ClinPred		0.091	T
GERP RS		-8.9
Varity_R		0.051
gMVP		0.36
Mutation Taster		=100/0	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

dbSNP: rs748073569; hg19: chr1-120436881;