Variant 10-126036268-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001288973.2(ADAM12):c.2407G>A(p.Gly803Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,558,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ADAM12
NM_001288973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.220

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032021165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADAM12	NM_001288973.2 link	c.2407G>A	p.Gly803Ser	missense_variant	21/23	ENST00000448723.2	NP_001275902.1
ADAM12	NM_003474.6 link	c.2416G>A	p.Gly806Ser	missense_variant	21/23		NP_003465.3
ADAM12	XM_017016706.2 link	c.1249G>A	p.Gly417Ser	missense_variant	11/13		XP_016872195.1
ADAM12	XM_024448210.1 link	c.1078G>A	p.Gly360Ser	missense_variant	10/12		XP_024303978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2 link	c.2407G>A	p.Gly803Ser	missense_variant	21/23	5	NM_001288973.2	ENSP00000391268.2		Q5JRP2
ADAM12	ENST00000368679.8 link	c.2416G>A	p.Gly806Ser	missense_variant	21/23	1		ENSP00000357668.4		O43184-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000999

AC:

AN:

200184

Hom.:

AF XY:

0.00000912

AC XY:

AN XY:

109688

show subpopulations

Gnomad AFR exome

AF:

0.0000779

Gnomad AMR exome

AF:

0.00

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:

0.000218

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1406528

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

698172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000339

Gnomad4 AMR exome

AF:

0.0000310

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000174

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Feb 28, 2023

The c.2416G>A (p.G806S) 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 2416, causing the glycine (G) at amino acid position 806 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.6

DANN

Benign

0.44

DEOGEN2

Benign

0.13

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.50

M_CAP

Benign

0.0047

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.28

PROVEAN

Benign

0.89

REVEL

Benign

0.041

Sift

Benign

0.74

Sift4G

Benign

1.0

Polyphen

0.022

Vest4

0.058

MVP

0.19

MPC

0.23

ClinPred

0.012

GERP RS

-2.1

Varity_R

0.027

gMVP

0.093

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