NM_001288973.2:c.416+1002A>C

Variant names:

• chr10-126134582-T-G
• rs1278329
• NM_001288973.2:c.416+1002A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

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.416+1002A>C		intron	N/A	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.425+1002A>C		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.425+1002A>C		intron	N/A	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.416+1002A>C		intron	N/A	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.425+1002A>C		intron	N/A	ENSP00000357668.4	O43184-1
	ADAM12	ENST00000368676.8	TSL:1	c.425+1002A>C		intron	N/A	ENSP00000357665.4	O43184-2

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

African (AFR) AF: 0.527 AC: 21825 AN: 41412

American (AMR) AF: 0.451 AC: 6886 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1262 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2483 AN: 5170

South Asian (SAS) AF: 0.374 AC: 1804 AN: 4820

European-Finnish (FIN) AF: 0.472 AC: 4995 AN: 10582

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28945 AN: 67958

Other (OTH) AF: 0.416 AC: 878 AN: 2112

Alfa AF: 0.441 Hom.: 29961

Bravo AF: 0.460

Asia WGS AF: 0.430 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		-0.54
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: rs1278329; hg19: chr10-127823151;