NM_001288973.2:c.261-53549_261-53548dupAA

Variant names:

• chr10-126208852-G-GTT
• rs5788775
• NM_001288973.2:c.261-53549_261-53548dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001288973.2(ADAM12):​c.261-53549_261-53548dupAA 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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.261-53549_261-53548dupAA		intron_variant	Intron 3 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-53548_261-53547insAA		intron_variant	Intron 3 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.261-53548_261-53547insAA		intron_variant	Intron 3 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.261-53548_261-53547insAA		intron_variant	Intron 3 of 18	1		ENSP00000357665.4

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

African (AFR) AF: 0.0549 AC: 2186 AN: 39816

American (AMR) AF: 0.0491 AC: 719 AN: 14652

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 177 AN: 3400

East Asian (EAS) AF: 0.0546 AC: 272 AN: 4978

South Asian (SAS) AF: 0.0524 AC: 237 AN: 4522

European-Finnish (FIN) AF: 0.0481 AC: 415 AN: 8628

Middle Eastern (MID) AF: 0.0423 AC: 12 AN: 284

European-Non Finnish (NFE) AF: 0.0390 AC: 2590 AN: 66358

Other (OTH) AF: 0.0377 AC: 76 AN: 2016

Alfa AF: 0.0377 Hom.: 1781

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5788775; hg19: chr10-127897421;