Genetic Variant ADAM23:p.Ala37Val (chr2-206443976-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003812.4(ADAM23):c.110C>T(p.Ala37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000923 in 1,369,442 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

ADAM23
NM_003812.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028658062).

BS2

High AC in GnomAd4 at 97 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003812.4. 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
	ADAM23	NM_003812.4	MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.110C>T	p.Ala37Val	missense	Exon 1 of 26	NP_001397914.1	E7EWD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAM23	ENST00000264377.8	TSL:1 MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 26	ENSP00000264377.3	O75077-1
ADAM23	ENST00000944282.1		c.110C>T	p.Ala37Val	missense	Exon 1 of 26	ENSP00000614341.1
ADAM23	ENST00000944276.1		c.110C>T	p.Ala37Val	missense	Exon 1 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes

AF:

0.000640

AC:

AN:

151606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000959

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000512

AC:

AN:

58570

AF XY:

0.000647

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.000571

GnomAD4 exome

AF:

0.000958

AC:

1167

AN:

1217734

Hom.:

Cov.:

AF XY:

0.000869

AC XY:

519

AN XY:

597172

show subpopulations

African (AFR)

AF:

0.0000791

AC:

AN:

25296

American (AMR)

AF:

0.0000939

AC:

AN:

21298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19906

East Asian (EAS)

AF:

0.00

AC:

AN:

26940

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54038

European-Finnish (FIN)

AF:

0.000143

AC:

AN:

28044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3470

European-Non Finnish (NFE)

AF:

0.00114

AC:

1128

AN:

989770

Other (OTH)

AF:

0.000613

AC:

AN:

48972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000639

AC:

AN:

151708

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41484

American (AMR)

AF:

0.000131

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000959

AC:

AN:

10426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

67838

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000847

Hom.:

Bravo

AF:

0.000601

ExAC

AF:

0.0000642

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.50

M_CAP

Benign

0.0067

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.34

PhyloP100

0.31

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.37

REVEL

Benign

0.036

Sift

Benign

0.084

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.11

MVP

0.18

MPC

1.4

ClinPred

0.066

GERP RS

1.4

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.057

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(source)

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

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