12-120345616-G-A

Variant names:

• chr12-120345616-G-A
• rs1350658498
• NM_002442.4:c.1064C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002442.4(MSI1):​c.1064C>T​(p.Thr355Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MSI1 NM_002442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI1	NM_002442.4	MANE Select	c.1064C>T	p.Thr355Ile	missense	Exon 14 of 15	NP_002433.1	O43347
	MSI1	NM_001414485.1		c.1061C>T	p.Thr354Ile	missense	Exon 14 of 15	NP_001401414.1
	MSI1	NM_001414486.1		c.1031C>T	p.Thr344Ile	missense	Exon 14 of 15	NP_001401415.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI1	ENST00000257552.7	TSL:1 MANE Select	c.1064C>T	p.Thr355Ile	missense	Exon 14 of 15	ENSP00000257552.2	O43347
	MSI1	ENST00000923996.1		c.1118C>T	p.Thr373Ile	missense	Exon 15 of 16	ENSP00000594055.1
	MSI1	ENST00000854931.1		c.1064C>T	p.Thr355Ile	missense	Exon 14 of 15	ENSP00000524990.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		9.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.47		Gain of catalytic residue at T358 (P = 2e-04)
MVP		0.31
MPC		2.0
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.44
gMVP		0.81
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1350658498; hg19: chr12-120783419;