chr19-4345946-C-T

Variant summary

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

The NM_001300862.2(MPND):​c.496C>T​(p.His166Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

MPND
NM_001300862.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10569686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPNDNM_001300862.2 linkc.496C>T p.His166Tyr missense_variant Exon 3 of 13 ENST00000599840.6 NP_001287791.1 W4VSR2
MPNDNM_032868.6 linkc.496C>T p.His166Tyr missense_variant Exon 3 of 12 NP_116257.2 Q8N594-1
MPNDNM_001159846.3 linkc.496C>T p.His166Tyr missense_variant Exon 3 of 11 NP_001153318.1 Q8N594-2
MPNDXM_006722926.3 linkc.496C>T p.His166Tyr 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.496C>T p.His166Tyr 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

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.496C>T (p.H166Y) alteration is located in exon 3 (coding exon 3) of the MPND gene. This alteration results from a C to T substitution at nucleotide position 496, causing the histidine (H) at amino acid position 166 to be replaced by a tyrosine (Y). 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
0.14
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Benign
0.50
DEOGEN2
Benign
0.0086
T;.;.;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.5
L;L;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.9
N;N;.;.
REVEL
Benign
0.057
Sift
Benign
0.60
T;T;.;.
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.0080
B;B;.;.
Vest4
0.27
MutPred
0.30
Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);.;
MVP
0.43
MPC
0.49
ClinPred
0.16
T
GERP RS
3.2
Varity_R
0.045
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4345943; API