Genetic Variant ADAM23:p.Arg61Gly (chr2-206444047-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003812.4(ADAM23):c.181C>G(p.Arg61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,250,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ADAM23
NM_003812.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.660

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.099390894).

BS2

High AC in GnomAdExome4 at 13 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.181C>G	p.Arg61Gly	missense	Exon 1 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.181C>G	p.Arg61Gly	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.181C>G	p.Arg61Gly	missense	Exon 1 of 26	ENSP00000264377.3	O75077-1
ADAM23	ENST00000944282.1		c.181C>G	p.Arg61Gly	missense	Exon 1 of 26	ENSP00000614341.1
ADAM23	ENST00000944276.1		c.181C>G	p.Arg61Gly	missense	Exon 1 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1250996

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

615732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26124

American (AMR)

AF:

0.00

AC:

AN:

23814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21096

East Asian (EAS)

AF:

0.00

AC:

AN:

27872

South Asian (SAS)

AF:

0.0000333

AC:

AN:

60120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4152

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1007614

Other (OTH)

AF:

0.00

AC:

AN:

50750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.75

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

-0.66

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.27

REVEL

Benign

0.082

Sift

Benign

0.68

Sift4G

Benign

0.37

Polyphen

0.093

Vest4

0.14

MutPred

0.44

Gain of glycosylation at S60 (P = 0.0523)

MVP

0.38

MPC

1.8

ClinPred

0.19

GERP RS

3.5

PromoterAI

0.060

Neutral

(source)

Varity_R

0.12

gMVP

0.24

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over