10-126145997-T-C

Variant names:

• chr10-126145997-T-C
• rs11244841
• NM_001288973.2:c.339+9230A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):​c.339+9230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,230 control chromosomes in the GnomAD database, including 3,428 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3428 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.339+9230A>G		intron_variant	Intron 4 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.339+9230A>G		intron_variant	Intron 4 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.348+9221A>G		intron_variant	Intron 4 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.348+9221A>G		intron_variant	Intron 4 of 18	1		ENSP00000357665.4
ADAM12	ENST00000494661.1	n.79+9230A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30235 AN: 152112 Hom.: 3422 Cov.: 33

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30261 AN: 152230 Hom.: 3428 Cov.: 33 AF XY: 0.193 AC XY: 14396 AN XY: 74426

African (AFR) AF: 0.0927 AC: 3853 AN: 41550

American (AMR) AF: 0.235 AC: 3590 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 793 AN: 3466

East Asian (EAS) AF: 0.150 AC: 778 AN: 5182

South Asian (SAS) AF: 0.150 AC: 726 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2147 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17663 AN: 68008

Other (OTH) AF: 0.208 AC: 440 AN: 2114

Alfa AF: 0.238 Hom.: 15150

Bravo AF: 0.200

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.29
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11244841; hg19: chr10-127834566;