rs10878804

chr12-68275477-G-Cchr12-68275477-G-T

Variant summary

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

The ENST00000357874.3(MDM1):c.*211+2147C>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,164 control chromosomes in the GnomAD database, including 3,228 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 0.19 (3228 hom., cov: 32)
• Consequence: MDM1 ENST00000357874.3 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDM1	ENST00000357874.3	c.*211+2147C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28505 AN: 152046 Hom.: 3224 Cov.: 32

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.187 AC: 28520 AN: 152164 Hom.: 3228 Cov.: 32 AF XY: 0.188 AC XY: 13973 AN XY: 74372

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.239

Alfa AF: 0.0914 Hom.: 130

Bravo AF: 0.190

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.21
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10878804; hg19: chr12-68669257;