10-126241146-G-C

Variant names:

• chr10-126241146-G-C
• rs4962528
• NM_001288973.2:c.260+37769C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001288973.2(ADAM12):​c.260+37769C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.260+37769C>G		intron	N/A	NP_001275902.1
	ADAM12	NM_003474.6		c.260+37769C>G		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.260+37769C>G		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.260+37769C>G		intron	N/A	ENSP00000391268.2
	ADAM12	ENST00000368679.8	TSL:1	c.260+37769C>G		intron	N/A	ENSP00000357668.4
	ADAM12	ENST00000368676.8	TSL:1	c.260+37769C>G		intron	N/A	ENSP00000357665.4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.088
PhyloP100		-0.12

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: rs4962528; hg19: chr10-127929715;