dbSNP rs372519061: MPND:p.Asp23Glu (chr19-4343769-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001300862.2(MPND):c.69C>G(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,208,520 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

MPND
NM_001300862.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056322068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300862.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPND	NM_001300862.2	MANE Select	c.69C>G	p.Asp23Glu	missense	Exon 2 of 13	NP_001287791.1	W4VSR2
MPND	NM_032868.6		c.69C>G	p.Asp23Glu	missense	Exon 2 of 12	NP_116257.2
MPND	NM_001159846.3		c.69C>G	p.Asp23Glu	missense	Exon 2 of 11	NP_001153318.1	Q8N594-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPND	ENST00000599840.6	TSL:5 MANE Select	c.69C>G	p.Asp23Glu	missense	Exon 2 of 13	ENSP00000471735.1	W4VSR2
MPND	ENST00000262966.12	TSL:1	c.69C>G	p.Asp23Glu	missense	Exon 2 of 12	ENSP00000262966.7	Q8N594-1
MPND	ENST00000594716.5	TSL:1	n.69C>G		non_coding_transcript_exon	Exon 2 of 12	ENSP00000470987.1	M0R044

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

166

AN:

150848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000924

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:

0.000962

GnomAD2 exomes

AF:

0.00

AC:

AN:

2042

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000728

AC:

AN:

1057564

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

500318

show subpopulations

African (AFR)

AF:

0.00312

AC:

AN:

21776

American (AMR)

AF:

0.000402

AC:

AN:

7456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12868

East Asian (EAS)

AF:

0.00

AC:

AN:

23858

South Asian (SAS)

AF:

0.00

AC:

AN:

19404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2754

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

904592

Other (OTH)

AF:

0.000120

AC:

AN:

41530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00110

AC:

166

AN:

150956

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

73786

show subpopulations

African (AFR)

AF:

0.00362

AC:

150

AN:

41408

American (AMR)

AF:

0.000923

AC:

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67514

Other (OTH)

AF:

0.000952

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.00114

ESP6500AA

AF:

0.00139

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000864

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0017

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

PhyloP100

-0.14

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.97

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.43

Polyphen

0.0020

Vest4

0.071

MutPred

0.089

Gain of helix (P = 0.027)

MVP

0.48

MPC

1.8

ClinPred

0.49

GERP RS

-3.4

PromoterAI

0.24

Neutral

(source)

Varity_R

0.30

gMVP

0.031

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over