14-24215628-C-T

Variant names:

• chr14-24215628-C-T
• rs770826445
• NM_138476.4:c.133G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138476.4(MDP1):​c.133G>A​(p.Val45Ile) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V45F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDP1 NM_138476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070111394).

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.133G>A	p.Val45Ile	missense	Exon 3 of 6	NP_612485.2
	NEDD8-MDP1	NM_001199823.3		c.184G>A	p.Val62Ile	missense	Exon 4 of 7	NP_001186752.1
	MDP1	NM_001199822.2		c.133G>A	p.Val45Ile	missense	Exon 3 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.133G>A	p.Val45Ile	missense	Exon 3 of 6	ENSP00000288087.7	Q86V88-1
	NEDD8-MDP1	ENST00000534348.5	TSL:5	c.184G>A	p.Val62Ile	missense	Exon 4 of 7	ENSP00000431482.1	E9PL57
	MDP1	ENST00000396833.2	TSL:1	c.133G>A	p.Val45Ile	missense	Exon 3 of 5	ENSP00000380045.2	Q86V88-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.75
DANN	Benign	0.92
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0050	N
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.070	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	-0.010	N
PhyloP100		-0.64
PROVEAN	Benign	0.0	N
REVEL	Benign	0.15
Sift	Benign	0.72	T
Sift4G	Benign	0.80	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.37		Gain of catalytic residue at L47 (P = 0.0107)
MVP		0.52
MPC		0.12
ClinPred		0.22	T
GERP RS		-4.3
PromoterAI		-0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.10
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs770826445; hg19: chr14-24684834;