19-757425-C-T

Variant summary

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

The ENST00000215582.8(MISP):​c.479C>T​(p.Thr160Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,597,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MISP
ENST00000215582.8 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.601
Variant links:
Genes affected
MISP (HGNC:27000): (mitotic spindle positioning) The protein encoded by this gene is an actin-bundling protein involved in determining cell morphology and mitotic progression. The encoded protein is required for the proper positioning of the mitotic spindle. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

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=0.16878399).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MISPNM_173481.4 linkuse as main transcriptc.479C>T p.Thr160Met missense_variant 2/5 ENST00000215582.8 NP_775752.1 Q8IVT2
MISPXM_011527685.3 linkuse as main transcriptc.479C>T p.Thr160Met missense_variant 2/5 XP_011525987.1 Q8IVT2
MISPXM_011527686.3 linkuse as main transcriptc.479C>T p.Thr160Met missense_variant 2/5 XP_011525988.1 Q8IVT2
MISPNR_135168.2 linkuse as main transcriptn.61-2484C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MISPENST00000215582.8 linkuse as main transcriptc.479C>T p.Thr160Met missense_variant 2/51 NM_173481.4 ENSP00000215582.4 Q8IVT2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000233
AC:
5
AN:
214710
Hom.:
0
AF XY:
0.0000258
AC XY:
3
AN XY:
116340
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000337
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000640
Gnomad SAS exome
AF:
0.0000358
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000209
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000152
AC:
22
AN:
1445588
Hom.:
0
Cov.:
33
AF XY:
0.0000181
AC XY:
13
AN XY:
717772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000245
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000514
Gnomad4 SAS exome
AF:
0.0000712
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000109
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152164
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00000828
AC:
1

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 GeneticsJan 19, 2024The c.479C>T (p.T160M) alteration is located in exon 2 (coding exon 1) of the MISP gene. This alteration results from a C to T substitution at nucleotide position 479, causing the threonine (T) at amino acid position 160 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
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.068
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.59
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.12
Sift
Benign
0.044
D
Sift4G
Uncertain
0.059
T
Polyphen
0.96
P
Vest4
0.20
MVP
0.36
MPC
0.17
ClinPred
0.18
T
GERP RS
2.0
Varity_R
0.049
gMVP
0.12

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: rs374036064; hg19: chr19-757425; API