Genetic Variant MSI1:p.Lys177Thr (chr12-120357820-T-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002442.4(MSI1):c.530A>C(p.Lys177Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MSI1
NM_002442.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

Publications

0 publications found

Variant links:

Genes affected

MSI1 (HGNC:7330): (musashi RNA binding protein 1) This gene encodes a protein containing two conserved tandem RNA recognition motifs. Similar proteins in other species function as RNA-binding proteins and play central roles in posttranscriptional gene regulation. Expression of this gene has been correlated with the grade of the malignancy and proliferative activity in gliomas and melanomas. A pseudogene for this gene is located on chromosome 11q13. [provided by RefSeq, Jul 2008]

MSI1 Gene-Disease associations (from GenCC):

microcephaly
Inheritance: AR Classification: LIMITED Submitted by: G2P

MSI1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002442.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSI1	NM_002442.4	MANE Select	c.530A>C	p.Lys177Thr	missense	Exon 8 of 15	NP_002433.1	O43347
MSI1	NM_001414485.1		c.527A>C	p.Lys176Thr	missense	Exon 8 of 15	NP_001401414.1
MSI1	NM_001414486.1		c.530A>C	p.Lys177Thr	missense	Exon 8 of 15	NP_001401415.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSI1	ENST00000257552.7	TSL:1 MANE Select	c.530A>C	p.Lys177Thr	missense	Exon 8 of 15	ENSP00000257552.2	O43347
MSI1	ENST00000923996.1		c.530A>C	p.Lys177Thr	missense	Exon 8 of 16	ENSP00000594055.1
MSI1	ENST00000854931.1		c.530A>C	p.Lys177Thr	missense	Exon 8 of 15	ENSP00000524990.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251312

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.29

MutationAssessor

Uncertain

2.6

PhyloP100

7.6

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.94

Vest4

0.86

MutPred

0.62

Loss of ubiquitination at K177 (P = 0.0218)

MVP

0.87

MPC

2.2

ClinPred

0.99

GERP RS

4.8

Varity_R

0.81

gMVP

0.80

Mutation Taster

=41/59

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over