14-24214105-T-G

Position:

chr14-24214105-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001199821.2(MDP1):c.310A>C(p.Lys104Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MDP1
NM_001199821.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.193

Variant links:

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]

MDP1 links:

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]

NEDD8-MDP1 links:

ENSG00000260669 (HGNC:):

ENSG00000260669 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13715887).

BP6

Variant 14-24214105-T-G is Benign according to our data. Variant chr14-24214105-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3293898.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDP1	NM_138476.4 linkuse as main transcript	c.450A>C	p.Leu150Leu	synonymous_variant	6/6	ENST00000288087.12	NP_612485.2	Q86V88-1
MDP1	NM_001199821.2 linkuse as main transcript	c.310A>C	p.Lys104Gln	missense_variant	5/5		NP_001186750.1	Q86V88-3
NEDD8-MDP1	NM_001199823.3 linkuse as main transcript	c.501A>C	p.Leu167Leu	synonymous_variant	7/7		NP_001186752.1
MDP1	NM_001199822.2 linkuse as main transcript	c.*84A>C		3_prime_UTR_variant	6/6		NP_001186751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDP1	ENST00000288087.12 linkuse as main transcript	c.450A>C	p.Leu150Leu	synonymous_variant	6/6	1	NM_138476.4	ENSP00000288087.7		Q86V88-1
NEDD8-MDP1	ENST00000534348.5 linkuse as main transcript	c.501A>C	p.Leu167Leu	synonymous_variant	7/7	5		ENSP00000431482.1		E9PL57

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Benign

8.5

DANN

Uncertain

0.98

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.52

M_CAP

Benign

0.0084

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.1

REVEL

Benign

0.035

Sift

Benign

0.039

Sift4G

Benign

0.070

Polyphen

0.016

Vest4

0.24

MutPred

0.24

Gain of catalytic residue at R106 (P = 0.0039);

MVP

0.28

ClinPred

0.31

GERP RS

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over