Variant 10-126036234-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001288973.2(ADAM12):c.2441G>A(p.Arg814Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,551,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ADAM12
NM_001288973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

Variant links:

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are 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. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ADAM12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19149655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAM12	NM_001288973.2 linkuse as main transcript	c.2441G>A	p.Arg814Gln	missense_variant	21/23	ENST00000448723.2	NP_001275902.1
ADAM12	NM_003474.6 linkuse as main transcript	c.2450G>A	p.Arg817Gln	missense_variant	21/23		NP_003465.3
ADAM12	XM_017016706.2 linkuse as main transcript	c.1283G>A	p.Arg428Gln	missense_variant	11/13		XP_016872195.1
ADAM12	XM_024448210.1 linkuse as main transcript	c.1112G>A	p.Arg371Gln	missense_variant	10/12		XP_024303978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2 linkuse as main transcript	c.2441G>A	p.Arg814Gln	missense_variant	21/23	5	NM_001288973.2	ENSP00000391268.2		Q5JRP2
ADAM12	ENST00000368679.8 linkuse as main transcript	c.2450G>A	p.Arg817Gln	missense_variant	21/23	1		ENSP00000357668.4		O43184-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000153

AC:

AN:

196438

Hom.:

AF XY:

0.00000927

AC XY:

AN XY:

107822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000969

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:

0.00

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1399276

Hom.:

Cov.:

AF XY:

0.00000865

AC XY:

AN XY:

693886

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000630

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00000644

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

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

Jan 04, 2024

The c.2450G>A (p.R817Q) alteration is located in exon 21 (coding exon 21) of the ADAM12 gene. This alteration results from a G to A substitution at nucleotide position 2450, causing the arginine (R) at amino acid position 817 to be replaced by a glutamine (Q). 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

0.083

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.073

Eigen_PC

Benign

0.0044

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.020

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.086

Sift

Benign

0.062

Sift4G

Benign

0.34

Polyphen

0.73

Vest4

0.36

MVP

0.43

MPC

0.73

ClinPred

0.83

GERP RS

4.2

Varity_R

0.091

gMVP

0.21

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