rs368803417

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001300862.2(MPND):​c.370C>A​(p.Pro124Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P124S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MPND
NM_001300862.2 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.17
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPNDNM_001300862.2 linkc.370C>A p.Pro124Thr missense_variant Exon 3 of 13 ENST00000599840.6 NP_001287791.1 W4VSR2
MPNDNM_032868.6 linkc.370C>A p.Pro124Thr missense_variant Exon 3 of 12 NP_116257.2 Q8N594-1
MPNDNM_001159846.3 linkc.370C>A p.Pro124Thr missense_variant Exon 3 of 11 NP_001153318.1 Q8N594-2
MPNDXM_006722926.3 linkc.370C>A p.Pro124Thr missense_variant Exon 3 of 13 XP_006722989.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MPNDENST00000599840.6 linkc.370C>A p.Pro124Thr missense_variant Exon 3 of 13 5 NM_001300862.2 ENSP00000471735.1 W4VSR2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.;.;.
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.7
M;M;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-7.9
D;D;.;.
REVEL
Uncertain
0.62
Sift
Pathogenic
0.0
D;D;.;.
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.86
MutPred
0.49
Loss of glycosylation at P124 (P = 0.0601);Loss of glycosylation at P124 (P = 0.0601);Loss of glycosylation at P124 (P = 0.0601);.;
MVP
0.77
MPC
1.3
ClinPred
1.0
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.86
gMVP
0.79

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.

Other links and lift over

dbSNP: rs368803417; hg19: chr19-4345817; API