Genetic Variant ADAM12:p.Ala822Ser (chr10-126036211-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001288973.2(ADAM12):c.2464G>T(p.Ala822Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAM12
NM_001288973.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052568763).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288973.2. 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
	ADAM12	NM_001288973.2	MANE Select	c.2464G>T	p.Ala822Ser	missense	Exon 21 of 23	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.2473G>T	p.Ala825Ser	missense	Exon 21 of 23	NP_003465.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.2464G>T	p.Ala822Ser	missense	Exon 21 of 23	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.2473G>T	p.Ala825Ser	missense	Exon 21 of 23	ENSP00000357668.4	O43184-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1395980

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691944

African (AFR)

AF:

0.00

AC:

AN:

29110

American (AMR)

AF:

0.00

AC:

AN:

31958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24324

East Asian (EAS)

AF:

0.00

AC:

AN:

34410

South Asian (SAS)

AF:

0.00

AC:

AN:

76720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084650

Other (OTH)

AF:

0.00

AC:

AN:

57564

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.14

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.64

M_CAP

Benign

0.0033

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PhyloP100

0.24

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.42

REVEL

Benign

0.050

Sift

Benign

0.46

Sift4G

Benign

0.67

Polyphen

0.10

Vest4

0.11

MutPred

0.13

Gain of phosphorylation at A825 (P = 0.0061)

MVP

0.20

MPC

0.21

ClinPred

0.090

GERP RS

0.77

Varity_R

0.029

gMVP

0.10

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over