12-68274666-G-A

Variant names:

• chr12-68274666-G-A
• rs11611206
• ENST00000357874.3:n.*212-2134C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357874.3(MDM1):​n.*212-2134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,110 control chromosomes in the GnomAD database, including 1,884 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 0.15 (1884 hom., cov: 32)
• Consequence: MDM1 ENST00000357874.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 3 publications found

Genes affected

MDM1 (HGNC:29917): (Mdm1 nuclear protein) This gene encodes a microtubule-binding nuclear protein that localizes to the centrioles of dividing cells and differentiating multiciliated cells and negatively regulates centriole duplication. The encoded protein is closely associated with the centriole barrel, and resides in the centriole lumen. Naturally-occurring mutations in the orthologous mouse gene are associated with age-related retinal degeneration. [provided by RefSeq, Feb 2019]

MDM1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000303715 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357874.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDM1	ENST00000357874.3	TSL:5	n.*212-2134C>T		intron	N/A	ENSP00000350544.3
	ENSG00000303715	ENST00000796708.1		n.134+9877G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23384 AN: 151990 Hom.: 1884 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.154 AC: 23384 AN: 152110 Hom.: 1884 Cov.: 32 AF XY: 0.157 AC XY: 11701 AN XY: 74330

African (AFR) AF: 0.141 AC: 5855 AN: 41514

American (AMR) AF: 0.130 AC: 1988 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3466

East Asian (EAS) AF: 0.101 AC: 524 AN: 5176

South Asian (SAS) AF: 0.0911 AC: 438 AN: 4810

European-Finnish (FIN) AF: 0.266 AC: 2813 AN: 10562

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.154 AC: 10468 AN: 67984

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.115 Hom.: 357

Bravo AF: 0.149

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs11611206; hg19: chr12-68668446;