chr10-126330454-CCC-GCG

Variant names:

• chr10-126330454-CCC-GCG
• NM_001288973.2:c.142_144delGGGinsCGC
• ADAM12 p.Gly48Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001288973.2(ADAM12):​c.142_144delGGGinsCGC​(p.Gly48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM12 NM_001288973.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.142_144delGGGinsCGC	p.Gly48Arg	missense	N/A	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.142_144delGGGinsCGC	p.Gly48Arg	missense	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.142_144delGGGinsCGC	p.Gly48Arg	missense	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.142_144delGGGinsCGC	p.Gly48Arg	missense	N/A	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.142_144delGGGinsCGC	p.Gly48Arg	missense	N/A	ENSP00000357668.4	O43184-1
	ADAM12	ENST00000368676.8	TSL:1	c.142_144delGGGinsCGC	p.Gly48Arg	missense	N/A	ENSP00000357665.4	O43184-2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-128019023;