Variant 8-39211165-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_145004.7(ADAM32):c.1074T>A(p.Thr358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,597,412 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

ADAM32
NM_145004.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 8-39211165-T-A is Benign according to our data. Variant chr8-39211165-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658564.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM32	NM_145004.7 linkuse as main transcript	c.1074T>A	p.Thr358=	synonymous_variant	12/25	ENST00000379907.9	NP_659441.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADAM32	ENST00000379907.9 linkuse as main transcript	c.1074T>A	p.Thr358=	synonymous_variant	12/25	1	NM_145004.7	ENSP00000369238	P1
ADAM32	ENST00000519315.5 linkuse as main transcript	c.916-10445T>A		intron_variant		1		ENSP00000429422
ADAM32	ENST00000437682.6 linkuse as main transcript	c.937-10445T>A		intron_variant		2		ENSP00000405978
ADAM32	ENST00000518259.1 linkuse as main transcript	n.5663-10445T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00222

AC:

525

AN:

235994

Hom.:

AF XY:

0.00225

AC XY:

289

AN XY:

128400

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.0000976

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.00400

Gnomad OTH exome

AF:

0.00126

GnomAD4 exome

AF:

0.00422

AC:

6095

AN:

1445086

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

2929

AN XY:

718750

show subpopulations

Gnomad4 AFR exome

AF:

0.000645

Gnomad4 AMR exome

AF:

0.000144

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.00102

Gnomad4 NFE exome

AF:

0.00519

Gnomad4 OTH exome

AF:

0.00226

GnomAD4 genome

AF:

0.00234

AC:

357

AN:

152326

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00218

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ADAM32: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

DANN

Benign

0.32

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

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