10-126269960-C-T

Variant names:

• chr10-126269960-C-T
• rs12251014
• NM_001288973.2:c.260+8955G>A

Variant summary

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

The NM_001288973.2(ADAM12):​c.260+8955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,090 control chromosomes in the GnomAD database, including 7,355 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 0.31 (7355 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.260+8955G>A		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.260+8955G>A		intron_variant	Intron 3 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.260+8955G>A		intron_variant	Intron 3 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.260+8955G>A		intron_variant	Intron 3 of 18	1		ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46851 AN: 151972 Hom.: 7347 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.308 AC: 46908 AN: 152090 Hom.: 7355 Cov.: 32 AF XY: 0.309 AC XY: 22949 AN XY: 74350

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.308

Alfa AF: 0.322 Hom.: 16072

Bravo AF: 0.310

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.67

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: rs12251014; hg19: chr10-127958529;