10-126134582-T-G

Position:

• chr10-126134582-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):​c.416+1002A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,006 control chromosomes in the GnomAD database, including 16,110 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 0.46 (16110 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.416+1002A>C		intron_variant		ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.416+1002A>C		intron_variant		5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.425+1002A>C		intron_variant		1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.425+1002A>C		intron_variant		1		ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69457 AN: 151888 Hom.: 16085 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.457 AC: 69541 AN: 152006 Hom.: 16110 Cov.: 32 AF XY: 0.458 AC XY: 34059 AN XY: 74332

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.416

Alfa AF: 0.427 Hom.: 6660

Bravo AF: 0.460

Asia WGS AF: 0.430 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.42

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: rs1278329; hg19: chr10-127823151;