10-126208852-GTTTTT-GTTTTTT

Position:

• chr10-126208852-GTTTTT-GTTTTTT

Variant summary

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

The NM_001288973.2(ADAM12):​c.261-53548dupA 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 0.89 (58417 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 (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.261-53548dupA		intron_variant		ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-53548dupA		intron_variant		5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.261-53548dupA		intron_variant		1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.261-53548dupA		intron_variant		1		ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.892 AC: 130020 AN: 145774 Hom.: 58419 Cov.: 0

Gnomad AFR AF: 0.761

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.892 AC: 130035 AN: 145826 Hom.: 58417 Cov.: 0 AF XY: 0.893 AC XY: 63101 AN XY: 70668

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.915

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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;