rs2641348

Positions:

• chr1-119895261-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021794.4(ADAM30):​c.1076T>C​(p.Leu359Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,614,016 control chromosomes in the GnomAD database, including 14,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (3009 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11537 hom.)
• Consequence: ADAM30 NM_021794.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002504617).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM30	NM_021794.4	c.1076T>C	p.Leu359Pro	missense_variant	1/1	ENST00000369400.2	NP_068566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM30	ENST00000369400.2	c.1076T>C	p.Leu359Pro	missense_variant	1/1	6	NM_021794.4	ENSP00000358407.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25710 AN: 152034 Hom.: 2998 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.125 AC: 31436 AN: 251408 Hom.: 2693 AF XY: 0.125 AC XY: 16988 AN XY: 135884

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.0888

Gnomad ASJ exome AF: 0.0715

Gnomad EAS exome AF: 0.0296

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.116 AC: 169728 AN: 1461864 Hom.: 11537 Cov.: 32 AF XY: 0.118 AC XY: 85549 AN XY: 727234

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.0920

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.0222

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.169 AC: 25742 AN: 152152 Hom.: 3009 Cov.: 32 AF XY: 0.169 AC XY: 12588 AN XY: 74402

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.156

Alfa AF: 0.112 Hom.: 2816

Bravo AF: 0.170

TwinsUK AF: 0.103 AC: 383

ALSPAC AF: 0.107 AC: 413

ESP6500AA AF: 0.325 AC: 1431

ESP6500EA AF: 0.104 AC: 896

ExAC AF: 0.132 AC: 15974

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.013
DANN	Benign	0.45
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.032
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.081
MPC		0.19
ClinPred		0.012	T
GERP RS		-9.3
Varity_R		0.065
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs2641348; hg19: chr1-120437884; COSMIC: COSV65561625;