rs193921062

chr14-24214313-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138476.4(MDP1):c.400C>G(p.Leu134Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDP1 NM_138476.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.217

Genes affected

MDP1 (HGNC:28781): (magnesium dependent phosphatase 1) Predicted to enable acid phosphatase activity. Predicted to be involved in fructosamine metabolic process and peptidyl-tyrosine dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

NEDD8-MDP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDP1	NM_138476.4	c.400C>G	p.Leu134Val	missense_variant	5/6	ENST00000288087.12
NEDD8-MDP1	NR_137631.2	n.612C>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDP1	ENST00000288087.12	c.400C>G	p.Leu134Val	missense_variant	5/6	1	NM_138476.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	0.027
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.61	D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	-2.2	N;N
REVEL	Pathogenic	0.65
Sift	Benign	0.043	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.92	P;.
Vest4		0.55
MutPred		0.47		Gain of catalytic residue at K133 (P = 0);.;
MVP		0.81
MPC		0.42
ClinPred		0.91	D
GERP RS		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.94		Position offset: 1
DS_DL_spliceai		0.59		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs193921062; hg19: chr14-24683519; COSMIC: COSV51660088; COSMIC: COSV51660088;