NM_001288973.2:c.261-2740C>A

Variant names:

• chr10-126158045-G-T
• rs10901542
• NM_001288973.2:c.261-2740C>A

Variant summary

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

The NM_001288973.2(ADAM12):​c.261-2740C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,088 control chromosomes in the GnomAD database, including 31,609 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 0.63 (31609 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 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.261-2740C>A		intron	N/A	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.261-2740C>A		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.261-2740C>A		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.261-2740C>A		intron	N/A	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.261-2740C>A		intron	N/A	ENSP00000357668.4	O43184-1
	ADAM12	ENST00000368676.8	TSL:1	c.261-2740C>A		intron	N/A	ENSP00000357665.4	O43184-2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95980 AN: 151970 Hom.: 31596 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.631 AC: 96031 AN: 152088 Hom.: 31609 Cov.: 33 AF XY: 0.638 AC XY: 47445 AN XY: 74336

African (AFR) AF: 0.432 AC: 17922 AN: 41466

American (AMR) AF: 0.746 AC: 11412 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2545 AN: 3470

East Asian (EAS) AF: 0.768 AC: 3964 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3459 AN: 4816

European-Finnish (FIN) AF: 0.696 AC: 7371 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46970 AN: 67976

Other (OTH) AF: 0.667 AC: 1408 AN: 2112

Alfa AF: 0.647 Hom.: 4237

Bravo AF: 0.628

Asia WGS AF: 0.716 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		-0.59
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: rs10901542; hg19: chr10-127846614;