Variant 2-206443976-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/21 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

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 -8 ACMG points.

BP4

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

BS2

High AC in GnomAd at 97 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADAM23	NM_003812.4 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/26	ENST00000264377.8
ADAM23	NM_001410985.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/26
ADAM23	XM_005246932.4 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM23	ENST00000264377.8 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/26	1	NM_003812.4	P4	O75077-1
ADAM23	ENST00000374415.7 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/26	5		A1

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

GnomAD3 exomes

AF:

0.000512

AC:

AN:

58570

Hom.:

AF XY:

0.000647

AC XY:

AN XY:

33984

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000791

Gnomad4 AMR exome

AF:

0.0000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000143

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000639

AC:

AN:

151708

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000959

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000847

Hom.:

Bravo

AF:

0.000601

ExAC

AF:

0.0000642

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.110C>T (p.A37V) alteration is located in exon 1 (coding exon 1) of the ADAM23 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the alanine (A) at amino acid position 37 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.078

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.34

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.036

Sift

Benign

0.084

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0

B;.

Vest4

0.11

MVP

0.18

MPC

1.4

ClinPred

0.066

GERP RS

1.4

Varity_R

0.057

gMVP

0.23

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