10-126202323-C-T

Position:

• chr10-126202323-C-T

Variant summary

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

The NM_001288973.2(ADAM12):​c.261-47018G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,940 control chromosomes in the GnomAD database, including 8,053 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 0.30 (8053 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.261-47018G>A		intron_variant		ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-47018G>A		intron_variant		5	NM_001288973.2	ENSP00000391268	A2
ADAM12	ENST00000368676.8	c.261-47018G>A		intron_variant		1		ENSP00000357665	A2
ADAM12	ENST00000368679.8	c.261-47018G>A		intron_variant		1		ENSP00000357668	P2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45672 AN: 151820 Hom.: 8032 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.301 AC: 45738 AN: 151940 Hom.: 8053 Cov.: 33 AF XY: 0.300 AC XY: 22299 AN XY: 74248

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.299

Alfa AF: 0.106 Hom.: 198

Bravo AF: 0.320

Asia WGS AF: 0.285 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.58

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: rs2927501; hg19: chr10-127890892;