dbSNP rs372433561: ADAM32:p.Val29Ile (chr8-39118112-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_145004.7(ADAM32):c.85G>A(p.Val29Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000467 in 1,476,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

ADAM32
NM_145004.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011677235).

BP6

Variant 8-39118112-G-A is Benign according to our data. Variant chr8-39118112-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3145706.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145004.7. 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
	ADAM32	NM_145004.7	MANE Select	c.85G>A	p.Val29Ile	missense	Exon 2 of 25	NP_659441.4
	ADAM32	NM_001313994.1		c.159+10279G>A		intron	N/A	NP_001300923.1	Q8TC27

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAM32	ENST00000379907.9	TSL:1 MANE Select	c.85G>A	p.Val29Ile	missense	Exon 2 of 25	ENSP00000369238.4	Q8TC27
ADAM32	ENST00000519315.5	TSL:1	c.85G>A	p.Val29Ile	missense	Exon 2 of 19	ENSP00000429422.1	E7ER82
ADAM32	ENST00000864644.1		c.85G>A	p.Val29Ile	missense	Exon 2 of 24	ENSP00000534703.1

Frequencies

GnomAD3 genomes

AF:

0.0000667

AC:

AN:

150000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00168

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

108978

AF XY:

0.000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000755

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000223

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000437

AC:

AN:

1326846

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

653690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27482

American (AMR)

AF:

0.0000410

AC:

AN:

24396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23802

East Asian (EAS)

AF:

0.0000631

AC:

AN:

31708

South Asian (SAS)

AF:

0.000713

AC:

AN:

67336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.00000575

AC:

AN:

1043124

Other (OTH)

AF:

0.0000182

AC:

AN:

55034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000733

AC:

AN:

150110

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73148

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40844

American (AMR)

AF:

0.0000663

AC:

AN:

15074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00169

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67582

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.000143

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0020

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.68

M_CAP

Benign

0.0022

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.82

PhyloP100

-1.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.48

REVEL

Benign

0.048

Sift

Benign

0.38

Sift4G

Benign

0.79

Polyphen

0.0070

Vest4

0.096

MVP

0.040

MPC

0.048

ClinPred

0.027

GERP RS

-3.4

Varity_R

0.028

gMVP

0.38

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over