1-119894016-T-G

Variant names:

• chr1-119894016-T-G
• rs1306107558
• NM_021794.4:c.2321A>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.2321A>C​(p.Asn774Thr) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N774S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM30 NM_021794.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• 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=0.045981526).

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.2321A>C	p.Asn774Thr	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.2321A>C	p.Asn774Thr	missense	Exon 1 of 1	ENSP00000358407.1	Q9UKF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250846 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.68
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.26
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.0060
Sift	Benign	0.16	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.14
MutPred		0.18		Gain of phosphorylation at N774 (P = 0.0155)
MVP		0.095
MPC		0.10
ClinPred		0.081	T
GERP RS		-1.2
Varity_R		0.039
gMVP		0.041
Mutation Taster		=95/5	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: rs1306107558; hg19: chr1-120436639;