12-68326847-G-T

Position:

• chr12-68326847-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354969.2(MDM1):​c.308C>A​(p.Thr103Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MDM1 NM_001354969.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031569988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM1	NM_001354969.2	c.308C>A	p.Thr103Asn	missense_variant	3/15	ENST00000682720.1	NP_001341898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM1	ENST00000682720.1	c.308C>A	p.Thr103Asn	missense_variant	3/15		NM_001354969.2	ENSP00000507100	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.73
DEOGEN2	Benign	0.015	T;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.032	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.2	N;N;.;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.2	N;N;N;N
REVEL	Benign	0.035
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.40	T;T;.;T
Polyphen		0.0	B;.;.;B
Vest4		0.039
MutPred		0.10		Loss of phosphorylation at T103 (P = 0.0217);Loss of phosphorylation at T103 (P = 0.0217);.;Loss of phosphorylation at T103 (P = 0.0217);
MVP		0.055
MPC		0.051
ClinPred		0.036	T
GERP RS		0.26
Varity_R		0.032
gMVP		0.061

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: rs962976; hg19: chr12-68720627;