10-126208852-GTTTTT-GTTTTTTT

Position:

• chr10-126208852-GTTTTT-GTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001288973.2(ADAM12):​c.261-53548_261-53547insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (151 hom., cov: 0)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.261-53548_261-53547insAA		intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-53548_261-53547insAA		intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.261-53548_261-53547insAA		intron_variant		1		A2
ADAM12	ENST00000368679.8	c.261-53548_261-53547insAA		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6677 AN: 145506 Hom.: 150 Cov.: 0

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0459 AC: 6684 AN: 145562 Hom.: 151 Cov.: 0 AF XY: 0.0449 AC XY: 3169 AN XY: 70518

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5788775; hg19: chr10-127897421;