rs10901596

chr10-126333006-G-Achr10-126333006-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):c.89-2497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,982 control chromosomes in the GnomAD database, including 19,494 homozygotes. 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: 𝑓 0.50 (19494 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.89-2497C>T		intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.89-2497C>T		intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.89-2497C>T		intron_variant		1		A2
ADAM12	ENST00000368679.8	c.89-2497C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76403 AN: 151864 Hom.: 19485 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.503 AC: 76450 AN: 151982 Hom.: 19494 Cov.: 32 AF XY: 0.496 AC XY: 36854 AN XY: 74274

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.520

Alfa AF: 0.507 Hom.: 39341

Bravo AF: 0.511

Asia WGS AF: 0.347 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.080
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10901596; hg19: chr10-128021575;