17-2387055-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020310.3(MNT):​c.1595C>T​(p.Thr532Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000898 in 1,559,228 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

MNT
NM_020310.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41
Variant links:
Genes affected
MNT (HGNC:7188): (MAX network transcriptional repressor) The Myc/Max/Mad network comprises a group of transcription factors that co-interact to regulate gene-specific transcriptional activation or repression. This gene encodes a protein member of the Myc/Max/Mad network. This protein has a basic-Helix-Loop-Helix-zipper domain (bHLHzip) with which it binds the canonical DNA sequence CANNTG, known as the E box, following heterodimerization with Max proteins. This protein is likely a transcriptional repressor and an antagonist of Myc-dependent transcriptional activation and cell growth. This protein represses transcription by binding to DNA binding proteins at its N-terminal Sin3-interaction domain. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2705735).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MNTNM_020310.3 linkuse as main transcriptc.1595C>T p.Thr532Met missense_variant 6/6 ENST00000174618.5 NP_064706.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MNTENST00000174618.5 linkuse as main transcriptc.1595C>T p.Thr532Met missense_variant 6/61 NM_020310.3 ENSP00000174618 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
2
AN:
166680
Hom.:
0
AF XY:
0.0000226
AC XY:
2
AN XY:
88428
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000300
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000853
AC:
12
AN:
1406892
Hom.:
0
Cov.:
32
AF XY:
0.0000130
AC XY:
9
AN XY:
694762
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000272
Gnomad4 SAS exome
AF:
0.0000250
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000831
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152336
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000171
AC:
2

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 submitterclinical testingAmbry GeneticsJun 05, 2024The c.1595C>T (p.T532M) alteration is located in exon 6 (coding exon 6) of the MNT gene. This alteration results from a C to T substitution at nucleotide position 1595, causing the threonine (T) at amino acid position 532 to be replaced by a methionine (M). 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
0.17
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.26
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.095
D
MetaRNN
Benign
0.27
T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.38
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.024
D
Polyphen
0.96
D
Vest4
0.34
MVP
0.38
MPC
0.32
ClinPred
0.85
D
GERP RS
4.9
Varity_R
0.14
gMVP
0.57

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: rs528548579; hg19: chr17-2290349; API