chr14-24214314-T-A

Variant names:

• chr14-24214314-T-A
• NM_138476.4:c.399A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138476.4(MDP1):​c.399A>T​(p.Lys133Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDP1 NM_138476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0660
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2729383).

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.399A>T	p.Lys133Asn	missense	Exon 5 of 6	NP_612485.2
	NEDD8-MDP1	NM_001199823.3		c.450A>T	p.Lys150Asn	missense	Exon 6 of 7	NP_001186752.1
	MDP1	NM_001199822.2		c.399A>T	p.Lys133Asn	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.399A>T	p.Lys133Asn	missense	Exon 5 of 6	ENSP00000288087.7	Q86V88-1
	NEDD8-MDP1	ENST00000534348.5	TSL:5	c.450A>T	p.Lys150Asn	missense	Exon 6 of 7	ENSP00000431482.1	E9PL57
	MDP1	ENST00000396833.2	TSL:1	c.264-163A>T		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: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.51	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.066
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.29
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.75	P
Vest4		0.18
MutPred		0.41		Gain of catalytic residue at V136 (P = 2e-04)
MVP		0.77
MPC		0.21
ClinPred		0.76	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.11
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr14-24683520;