10-126093840-C-G

Variant names:

• chr10-126093840-C-G
• rs1871054
• NM_001288973.2:c.1145+145G>C

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.1145+145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,144,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 32 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.1145+145G>C		intron_variant	Intron 11 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.1145+145G>C		intron_variant	Intron 11 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.1154+145G>C		intron_variant	Intron 11 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.1154+145G>C		intron_variant	Intron 11 of 18	1		ENSP00000357665.4
ADAM12	ENST00000485388.2	n.124-2847G>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1144638 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 571998

African (AFR) AF: 0.00 AC: 0 AN: 26234

American (AMR) AF: 0.0000296 AC: 1 AN: 33812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19306

East Asian (EAS) AF: 0.00 AC: 0 AN: 37764

South Asian (SAS) AF: 0.00 AC: 0 AN: 67790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 862448

Other (OTH) AF: 0.0000204 AC: 1 AN: 49134

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		-0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1871054; hg19: chr10-127782409;