10-126330456-C-T

Position:

• chr10-126330456-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001288973.2(ADAM12):​c.142G>A​(p.Gly48Arg) 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. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM12 NM_001288973.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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]

ACMG classification

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=0.049088925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.142G>A	p.Gly48Arg	missense_variant	2/23	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.142G>A	p.Gly48Arg	missense_variant	2/23	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.142G>A	p.Gly48Arg	missense_variant	2/23	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.142G>A	p.Gly48Arg	missense_variant	2/19	1		ENSP00000357665.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461534 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 727078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0070
DANN	Benign	0.34
DEOGEN2	Benign	0.14	T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.76	T;T;T
Sift4G	Benign	0.63	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.028
MutPred		0.25		Gain of MoRF binding (P = 0.0578);Gain of MoRF binding (P = 0.0578);Gain of MoRF binding (P = 0.0578);
MVP		0.16
MPC		0.27
ClinPred		0.031	T
GERP RS		-3.9
Varity_R		0.033
gMVP		0.72

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

Other links and lift over

dbSNP: rs3740199; hg19: chr10-128019025; COSMIC: COSV64102688;