Variant 19-4343845-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001300862.2(MPND):c.145G>C(p.Val49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000462 in 1,211,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

MPND
NM_001300862.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

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 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=0.044932455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPND	NM_001300862.2 linkuse as main transcript	c.145G>C	p.Val49Leu	missense_variant	2/13	ENST00000599840.6	NP_001287791.1	W4VSR2
MPND	NM_032868.6 linkuse as main transcript	c.145G>C	p.Val49Leu	missense_variant	2/12		NP_116257.2	Q8N594-1
MPND	NM_001159846.3 linkuse as main transcript	c.145G>C	p.Val49Leu	missense_variant	2/11		NP_001153318.1	Q8N594-2
MPND	XM_006722926.3 linkuse as main transcript	c.145G>C	p.Val49Leu	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.145G>C	p.Val49Leu	missense_variant	2/13	5	NM_001300862.2	ENSP00000471735.1		W4VSR2

Frequencies

GnomAD3 genomes

AF:

0.0000930

AC:

AN:

150488

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000396

AC:

AN:

1061508

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

505452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00243

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000879

Gnomad4 OTH exome

AF:

0.0000721

GnomAD4 genome

AF:

0.0000930

AC:

AN:

150488

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

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

Mar 17, 2023

The c.145G>C (p.V49L) alteration is located in exon 2 (coding exon 2) of the MPND gene. This alteration results from a G to C substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by a leucine (L). 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

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0046

T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.46

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.34

N;N;.;.

REVEL

Benign

0.23

Sift

Benign

0.22

T;T;.;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.076

MutPred

0.16

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;

MVP

0.43

MPC

1.9

ClinPred

0.13

GERP RS

0.35

Varity_R

0.054

gMVP

0.20

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