Variant 22-43505522-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001044370.2(MPPED1):c.887C>T(p.Thr296Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MPPED1
NM_001044370.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Variant links:

Genes affected

MPPED1 (HGNC:1306): (metallophosphoesterase domain containing 1) Predicted to enable hydrolase activity. [provided by Alliance of Genome Resources, Apr 2022]

MPPED1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27275157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPPED1	NM_001044370.2 linkuse as main transcript	c.887C>T	p.Thr296Met	missense_variant	7/7	ENST00000443721.2	NP_001037835.1
MPPED1	NM_001362786.2 linkuse as main transcript	c.887C>T	p.Thr296Met	missense_variant	7/7		NP_001349715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPPED1	ENST00000443721.2 linkuse as main transcript	c.887C>T	p.Thr296Met	missense_variant	7/7	2	NM_001044370.2	ENSP00000400686	P1	O15442-1
MPPED1	ENST00000417669.6 linkuse as main transcript	c.887C>T	p.Thr296Met	missense_variant	7/7	5		ENSP00000388137	P1	O15442-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242908

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

131900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1458814

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.887C>T (p.T296M) alteration is located in exon 2 (coding exon 2) of the MPPED1 gene. This alteration results from a C to T substitution at nucleotide position 887, causing the threonine (T) at amino acid position 296 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.24

Sift

Benign

0.11

T;T

Sift4G

Benign

0.19

T;T

Polyphen

1.0

D;D

Vest4

0.41

MVP

0.59

MPC

1.4

ClinPred

0.26

GERP RS

3.3

Varity_R

0.065

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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