Variant 10-133263747-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001109.5(ADAM8):c.2338G>A(p.Ala780Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,569,702 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A780P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

ADAM8
NM_001109.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.520

Variant links:

Genes affected

ADAM8 (HGNC:215): (ADAM metallopeptidase domain 8) 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. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2009]

ADAM8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0060773194).

BP6

Variant 10-133263747-C-T is Benign according to our data. Variant chr10-133263747-C-T is described in ClinVar as [Benign]. Clinvar id is 786585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM8	NM_001109.5 linkuse as main transcript	c.2338G>A	p.Ala780Thr	missense_variant	22/23	ENST00000445355.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM8	ENST00000445355.8 linkuse as main transcript	c.2338G>A	p.Ala780Thr	missense_variant	22/23	1	NM_001109.5	P2	P78325-1
ADAM8	ENST00000415217.7 linkuse as main transcript	c.2171G>A	p.Arg724His	missense_variant	21/22	1		A2	P78325-3
ADAM8	ENST00000485491.6 linkuse as main transcript	c.2125-514G>A		intron_variant		2			P78325-2
ADAM8	ENST00000559018.1 linkuse as main transcript	n.119G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00756

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000505

AC:

AN:

189946

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

102798

show subpopulations

Gnomad AFR exome

AF:

0.00791

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000728

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000118

Gnomad OTH exome

AF:

0.000216

GnomAD4 exome

AF:

0.000190

AC:

269

AN:

1417410

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

108

AN XY:

702160

show subpopulations

Gnomad4 AFR exome

AF:

0.00659

Gnomad4 AMR exome

AF:

0.000260

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000811

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.000581

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152292

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00756

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000113

Hom.:

Bravo

AF:

0.00253

ESP6500AA

AF:

0.00682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000655

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.3

DANN

Benign

0.89

DEOGEN2

Benign

0.061

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0061

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.55

Sift

Benign

0.42

Sift4G

Benign

0.77

Polyphen

0.10

Vest4

0.10

MVP

0.48

MPC

0.12

GERP RS

-0.75

Varity_R

0.025

gMVP

0.092

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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