Variant 2-206445465-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003812.4(ADAM23):c.373T>G(p.Ser125Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00611 in 1,614,112 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 38 hom. )

Consequence

ADAM23
NM_003812.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.83

Variant links:

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) 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. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ADAM23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100236535).

BP6

Variant 2-206445465-T-G is Benign according to our data. Variant chr2-206445465-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 777961.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 881 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADAM23	NM_003812.4 linkuse as main transcript	c.373T>G	p.Ser125Ala	missense_variant	2/26	ENST00000264377.8
ADAM23	NM_001410985.1 linkuse as main transcript	c.373T>G	p.Ser125Ala	missense_variant	2/26
ADAM23	XM_005246932.4 linkuse as main transcript	c.373T>G	p.Ser125Ala	missense_variant	2/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM23	ENST00000264377.8 linkuse as main transcript	c.373T>G	p.Ser125Ala	missense_variant	2/26	1	NM_003812.4	P4	O75077-1
ADAM23	ENST00000374415.7 linkuse as main transcript	c.373T>G	p.Ser125Ala	missense_variant	2/26	5		A1

Frequencies

GnomAD3 genomes

AF:

0.00579

AC:

881

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00584

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00478

AC:

1202

AN:

251218

Hom.:

AF XY:

0.00486

AC XY:

660

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00749

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00614

AC:

8970

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

4348

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00439

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00949

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.000730

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.00659

GnomAD4 genome

AF:

0.00581

AC:

885

AN:

152288

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

416

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00592

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00741

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00643

Hom.:

Bravo

AF:

0.00612

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00498

AC:

605

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00622

EpiControl

AF:

0.00824

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.15

Sift

Benign

0.30

T;T

Sift4G

Benign

0.096

T;T

Polyphen

0.39

B;.

Vest4

0.48

MVP

0.26

MPC

0.25

ClinPred

0.023

GERP RS

4.8

Varity_R

0.088

gMVP

0.29

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