Genetic Variant ADAM32:c.-61_-54dupCGCGTCCC (chr8-39107706-G-GCGCGTCCC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001313994.1(ADAM32):c.41_48dupCGCGTCCC(p.Trp17ArgfsTer49) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,547,434 control chromosomes in the GnomAD database, including 89 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 19 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 70 hom. )

Consequence

ADAM32
NM_001313994.1 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.293

Variant links:

Genes affected

ADAM32 (HGNC:15479): (ADAM metallopeptidase domain 32) This gene encodes a member of the disintegrin family of membrane-anchored proteins that play a role in diverse biological processes such as brain development, fertilization, tumor development and inflammation. This gene is predominantly expressed in the testis. The encoded protein undergoes proteolytic processing to generate a mature polypeptide comprised of an metalloprotease, disintegrin and epidermal growth factor-like domains. This gene is located in a cluster of other disintegrin and metallopeptidase family genes on chromosome 8. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

ADAM32 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 8-39107706-G-GCGCGTCCC is Benign according to our data. Variant chr8-39107706-G-GCGCGTCCC is described in ClinVar as [Likely_benign]. Clinvar id is 3067238.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM32	NM_145004.7 link	c.-70_-69insCGCGTCCC		upstream_gene_variant		ENST00000379907.9	NP_659441.4	Q8TC27A0A140VJD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM32	ENST00000379907.9 link	c.-70_-69insCGCGTCCC		upstream_gene_variant		1	NM_145004.7	ENSP00000369238.4		Q8TC27

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

839

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00702

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00531

AC:

780

AN:

146956

Hom.:

AF XY:

0.00473

AC XY:

372

AN XY:

78616

show subpopulations

Gnomad AFR exome

AF:

0.000681

Gnomad AMR exome

AF:

0.000287

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00313

Gnomad SAS exome

AF:

0.000177

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.000902

Gnomad OTH exome

AF:

0.00356

GnomAD4 exome

AF:

0.00276

AC:

3850

AN:

1395378

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1845

AN XY:

688214

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.000281

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0146

Gnomad4 SAS exome

AF:

0.000215

Gnomad4 FIN exome

AF:

0.0473

Gnomad4 NFE exome

AF:

0.000741

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.00552

AC:

840

AN:

152056

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

597

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00703

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0568

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00446

Hom.:

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADAM32: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over