Genetic Variant NM_021794.4:c.1242C>T (chr1-119895095-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021794.4(ADAM30):c.1242C>T(p.Asp414Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,932 control chromosomes in the GnomAD database, including 31,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 8970 hom., cov: 32)

Exomes 𝑓: 0.15 ( 22325 hom. )

Consequence

ADAM30
NM_021794.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

Publications

29 publications found

Variant links:

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]

ADAM30 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-0.567 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM30	NM_021794.4 link	c.1242C>T	p.Asp414Asp	synonymous_variant	Exon 1 of 1	ENST00000369400.2	NP_068566.2	Q9UKF2-1Q8TBZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM30	ENST00000369400.2 link	c.1242C>T	p.Asp414Asp	synonymous_variant	Exon 1 of 1	6	NM_021794.4	ENSP00000358407.1		Q9UKF2-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41100

AN:

151994

Hom.:

8942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.188

AC:

47325

AN:

251240

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.0995

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.151

AC:

220172

AN:

1461820

Hom.:

22325

Cov.:

AF XY:

0.153

AC XY:

111451

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.622

AC:

20812

AN:

33480

American (AMR)

AF:

0.186

AC:

8317

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3053

AN:

26136

East Asian (EAS)

AF:

0.0672

AC:

2667

AN:

39700

South Asian (SAS)

AF:

0.288

AC:

24863

AN:

86254

European-Finnish (FIN)

AF:

0.178

AC:

9511

AN:

53362

Middle Eastern (MID)

AF:

0.174

AC:

1001

AN:

5768

European-Non Finnish (NFE)

AF:

0.125

AC:

139521

AN:

1112000

Other (OTH)

AF:

0.173

AC:

10427

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12392

24784

37177

49569

61961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5378

10756

16134

21512

26890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.271

AC:

41177

AN:

152112

Hom.:

8970

Cov.:

AF XY:

0.271

AC XY:

20143

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.601

AC:

24933

AN:

41452

American (AMR)

AF:

0.183

AC:

2789

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

423

AN:

3470

East Asian (EAS)

AF:

0.0955

AC:

494

AN:

5174

South Asian (SAS)

AF:

0.293

AC:

1413

AN:

4820

European-Finnish (FIN)

AF:

0.177

AC:

1878

AN:

10602

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8625

AN:

67996

Other (OTH)

AF:

0.245

AC:

516

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1204

2409

3613

4818

6022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

11997

Bravo

AF:

0.281

Asia WGS

AF:

0.299

AC:

1038

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.38

(source)

DANN

Benign

0.34

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over