Variant 22-43425049-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001044370.2(MPPED1):c.64G>A(p.Gly22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MPPED1
NM_001044370.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.688

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPPED1	NM_001044370.2 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	2/7	ENST00000443721.2	NP_001037835.1
MPPED1	NM_001362786.2 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	2/7		NP_001349715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPPED1	ENST00000443721.2 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	2/7	2	NM_001044370.2	ENSP00000400686	P1	O15442-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000816

AC:

AN:

245246

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460438

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Aug 30, 2021

The c.64G>A (p.G22S) alteration is located in exon (coding exon ) of the MPPED1 gene. This alteration results from a G to A substitution at nucleotide position 64, causing the glycine (G) at amino acid position 22 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0058

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.81

.;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.

MutationTaster

Benign

1.0

D;D;N;N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.52

N;N;N;N

REVEL

Benign

0.098

Sift

Uncertain

0.024

D;T;D;T

Sift4G

Pathogenic

0.0

D;T;D;T

Polyphen

0.0010

B;.;B;.

Vest4

0.20

MVP

0.67

MPC

0.82

ClinPred

0.31

GERP RS

3.0

Varity_R

0.069

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: 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