rs193921062

Variant names:

• chr14-24214313-G-C
• rs193921062
• NM_138476.4:c.400C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

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
• Publications: 0 publications found

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:39551): (NEDD8-MDP1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) and MDP1 (magnesium-dependent phosphatase 1) genes on chromosome 14. One of the read-through transcripts on this locus encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Jul 2016]

ENSG00000260669 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138476.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDP1	NM_138476.4	MANE Select	c.400C>G	p.Leu134Val	missense	Exon 5 of 6	NP_612485.2
	NEDD8-MDP1	NM_001199823.3		c.451C>G	p.Leu151Val	missense	Exon 6 of 7	NP_001186752.1
	MDP1	NM_001199822.2		c.400C>G	p.Leu134Val	missense	Exon 5 of 6	NP_001186751.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDP1	ENST00000288087.12	TSL:1 MANE Select	c.400C>G	p.Leu134Val	missense	Exon 5 of 6	ENSP00000288087.7	Q86V88-1
	NEDD8-MDP1	ENST00000534348.5	TSL:5	c.451C>G	p.Leu151Val	missense	Exon 6 of 7	ENSP00000431482.1	E9PL57
	MDP1	ENST00000396833.2	TSL:1	c.264-162C>G		intron	N/A	ENSP00000380045.2	Q86V88-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.22
PROVEAN	Benign	-2.2	N
REVEL	Pathogenic	0.65
Sift	Benign	0.043	D
Sift4G	Uncertain	0.034	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

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