rs3740199

Variant names:

• chr10-126330456-C-A
• rs3740199
• NM_001288973.2:c.142G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-126330456-C-A
• chr10-126330456-C-G
• chr10-126330456-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 59 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047103167).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.142G>T	p.Gly48Trp	missense	Exon 2 of 23	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.142G>T	p.Gly48Trp	missense	Exon 2 of 23	NP_003465.3
	ADAM12	NM_021641.5		c.142G>T	p.Gly48Trp	missense	Exon 2 of 19	NP_067673.2	O43184-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.142G>T	p.Gly48Trp	missense	Exon 2 of 23	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.142G>T	p.Gly48Trp	missense	Exon 2 of 23	ENSP00000357668.4	O43184-1
	ADAM12	ENST00000368676.8	TSL:1	c.142G>T	p.Gly48Trp	missense	Exon 2 of 19	ENSP00000357665.4	O43184-2

Frequencies

GnomAD3 genomes AF: 0.00203 AC: 309 AN: 151962 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00208 AC: 522 AN: 250642 AF XY: 0.00204

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 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.: 9 Cov.: 48 AF XY: 0.00337 AC XY: 2448 AN XY: 727072

African (AFR) AF: 0.000658 AC: 22 AN: 33452

American (AMR) AF: 0.000202 AC: 9 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86212

European-Finnish (FIN) AF: 0.00459 AC: 245 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00411 AC: 4574 AN: 1111918

Other (OTH) AF: 0.00242 AC: 146 AN: 60382

GnomAD4 genome AF: 0.00203 AC: 309 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74318

African (AFR) AF: 0.000603 AC: 25 AN: 41472

American (AMR) AF: 0.000458 AC: 7 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00284 AC: 30 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00356 AC: 242 AN: 67988

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00119 Hom.: 2877

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00597 AC: 23

ExAC AF: 0.00232 AC: 282

EpiCase AF: 0.00300

EpiControl AF: 0.00350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.011
DANN	Benign	0.30
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.061
Sift	Benign	0.10	T
Sift4G	Benign	0.077	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.11
MPC		0.27
ClinPred		0.0040	T
GERP RS		-3.9
Varity_R		0.030
gMVP		0.69
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3740199; hg19: chr10-128019025;