Variant 19-4343972-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001300862.2(MPND):c.272G>A(p.Gly91Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,482 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

MPND
NM_001300862.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Variant links:

Genes affected

MPND (HGNC:25934): (MPN domain containing) Predicted to enable histone binding activity; peptidase activity; and transcription coactivator activity. Predicted to be involved in chromatin remodeling and positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

MPND links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11384478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPND	NM_001300862.2 linkuse as main transcript	c.272G>A	p.Gly91Glu	missense_variant	2/13	ENST00000599840.6	NP_001287791.1	W4VSR2
MPND	NM_032868.6 linkuse as main transcript	c.272G>A	p.Gly91Glu	missense_variant	2/12		NP_116257.2	Q8N594-1
MPND	NM_001159846.3 linkuse as main transcript	c.272G>A	p.Gly91Glu	missense_variant	2/11		NP_001153318.1	Q8N594-2
MPND	XM_006722926.3 linkuse as main transcript	c.272G>A	p.Gly91Glu	missense_variant	2/13		XP_006722989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPND	ENST00000599840.6 linkuse as main transcript	c.272G>A	p.Gly91Glu	missense_variant	2/13	5	NM_001300862.2	ENSP00000471735.1		W4VSR2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00000244

AC:

AN:

1231328

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

605454

show subpopulations

Gnomad4 AFR exome

AF:

0.0000792

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:

0.00000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

ExAC

AF:

0.00000951

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

Oct 25, 2022

The c.272G>A (p.G91E) alteration is located in exon 2 (coding exon 2) of the MPND gene. This alteration results from a G to A substitution at nucleotide position 272, causing the glycine (G) at amino acid position 91 to be replaced by a glutamic acid (E). 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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;.;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.8

D;D;.;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.010

D;D;.;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.92

P;D;.;.

Vest4

0.46

MutPred

0.70

Loss of catalytic residue at V92 (P = 0.0447);Loss of catalytic residue at V92 (P = 0.0447);Loss of catalytic residue at V92 (P = 0.0447);.;

MVP

0.26

MPC

1.0

ClinPred

0.41

GERP RS

3.9

Varity_R

0.74

gMVP

0.78

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

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