10-126325188-G-T

Variant names:

• chr10-126325188-G-T
• rs7082342
• NM_001288973.2:c.186+5224C>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.186+5224C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,002 control chromosomes in the GnomAD database, including 33,686 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 0.66 (33686 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.722 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	NM_001288973.2	MANE Select	c.186+5224C>A		intron	N/A	NP_001275902.1
	ADAM12	NM_003474.6		c.186+5224C>A		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.186+5224C>A		intron	N/A	NP_067673.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.186+5224C>A		intron	N/A	ENSP00000391268.2
	ADAM12	ENST00000368679.8	TSL:1	c.186+5224C>A		intron	N/A	ENSP00000357668.4
	ADAM12	ENST00000368676.8	TSL:1	c.186+5224C>A		intron	N/A	ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100854 AN: 151884 Hom.: 33644 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.664 AC: 100953 AN: 152002 Hom.: 33686 Cov.: 32 AF XY: 0.666 AC XY: 49479 AN XY: 74298

African (AFR) AF: 0.663 AC: 27475 AN: 41464

American (AMR) AF: 0.733 AC: 11203 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2597 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3485 AN: 5146

South Asian (SAS) AF: 0.611 AC: 2938 AN: 4808

European-Finnish (FIN) AF: 0.695 AC: 7349 AN: 10576

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43650 AN: 67944

Other (OTH) AF: 0.667 AC: 1403 AN: 2102

Alfa AF: 0.664 Hom.: 4366

Bravo AF: 0.671

Asia WGS AF: 0.691 AC: 2401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.37
PhyloP100		-0.26
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: rs7082342; hg19: chr10-128013757;