chr12-68315199-G-A

Variant names:

• chr12-68315199-G-A
• rs139553308
• NM_001354969.2:c.1278C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001354969.2(MDM1):​c.1278C>T​(p.Ile426Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00935 in 1,614,090 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (108 hom.)
• Consequence: MDM1 NM_001354969.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500
• Publications: 4 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)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-68315199-G-A is Benign according to our data. Variant chr12-68315199-G-A is described in ClinVar as [Benign]. Clinvar id is 3024764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.5 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM1	NM_001354969.2	c.1278C>T	p.Ile426Ile	synonymous_variant	Exon 10 of 15	ENST00000682720.1	NP_001341898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM1	ENST00000682720.1	c.1278C>T	p.Ile426Ile	synonymous_variant	Exon 10 of 15		NM_001354969.2	ENSP00000507100.1

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 979 AN: 152102 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00500

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00732 AC: 1840 AN: 251438 AF XY: 0.00712

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00575

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00753

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00966 AC: 14118 AN: 1461870 Hom.: 108 Cov.: 34 AF XY: 0.00948 AC XY: 6894 AN XY: 727234

African (AFR) AF: 0.00173 AC: 58 AN: 33478

American (AMR) AF: 0.00145 AC: 65 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00517 AC: 135 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00235 AC: 203 AN: 86256

European-Finnish (FIN) AF: 0.00805 AC: 430 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0115 AC: 12831 AN: 1111994

Other (OTH) AF: 0.00649 AC: 392 AN: 60396

GnomAD4 genome AF: 0.00643 AC: 979 AN: 152220 Hom.: 6 Cov.: 32 AF XY: 0.00618 AC XY: 460 AN XY: 74442

African (AFR) AF: 0.00176 AC: 73 AN: 41528

American (AMR) AF: 0.00275 AC: 42 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.00500 AC: 53 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68020

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.00946 Hom.: 7

Bravo AF: 0.00601

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0100

EpiControl AF: 0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MDM1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs139553308; hg19: chr12-68708979;