chr14-24214311-CAG-TAC

Variant names:

• chr14-24214311-CAG-TAC
• NM_138476.4:c.400_402delCTGinsGTA
• MDP1 p.Leu134Val

Variant summary

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

The NM_138476.4(MDP1):​c.400_402delCTGinsGTA​(p.Leu134Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDP1 NM_138476.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• 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 0 ACMG points.

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.400_402delCTGinsGTA	p.Leu134Val	missense splice_region	N/A	NP_612485.2
	MDP1	NM_001199822.2		c.400_402delCTGinsGTA	p.Leu134Val	missense	N/A	NP_001186751.1
	NEDD8-MDP1	NM_001199823.3		c.451_453delCTGinsGTA	p.Leu151Val	missense splice_region	N/A	NP_001186752.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDP1	ENST00000288087.12	TSL:1 MANE Select	c.400_402delCTGinsGTA	p.Leu134Val	missense splice_region	N/A	ENSP00000288087.7	Q86V88-1
	NEDD8-MDP1	ENST00000534348.5	TSL:5	c.451_453delCTGinsGTA	p.Leu151Val	missense splice_region	N/A	ENSP00000431482.1	E9PL57
	MDP1	ENST00000396833.2	TSL:1	c.264-162_264-160delCTGinsGTA		intron	N/A	ENSP00000380045.2	Q86V88-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-24683517;