Variant chr10-126330456-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001288973.2(ADAM12):c.142G>T(p.Gly48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,613,608 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

ADAM12
NM_001288973.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047103167).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2 link	c.142G>T	p.Gly48Trp	missense_variant	2/23	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAM12	ENST00000448723.2 link	c.142G>T	p.Gly48Trp	missense_variant	2/23	5	NM_001288973.2	ENSP00000391268.2	Q5JRP2
ADAM12	ENST00000368679.8 link	c.142G>T	p.Gly48Trp	missense_variant	2/23	1		ENSP00000357668.4	O43184-1
ADAM12	ENST00000368676.8 link	c.142G>T	p.Gly48Trp	missense_variant	2/19	1		ENSP00000357665.4	O43184-2

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

309

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00208

AC:

522

AN:

250642

Hom.:

AF XY:

0.00204

AC XY:

276

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00343

AC:

5019

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

2448

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00459

Gnomad4 NFE exome

AF:

0.00411

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152080

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00284

Gnomad4 NFE

AF:

0.00356

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00144

Hom.:

2877

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00597

AC:

ExAC

AF:

0.00232

AC:

282

EpiCase

AF:

0.00300

EpiControl

AF:

0.00350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.011

DANN

Benign

0.30

DEOGEN2

Benign

0.16

T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.19

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.55

N;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.67

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.077

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.17

MVP

0.11

MPC

0.27

ClinPred

0.0040

GERP RS

-3.9

Varity_R

0.030

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over