Genetic Variant MSI1:c.*999A>C (chr12-120342128-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002442.4(MSI1):c.*999A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,928 control chromosomes in the GnomAD database, including 14,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 14409 hom., cov: 30)

Exomes 𝑓: 0.50 ( 156 hom. )

Consequence

MSI1
NM_002442.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.414

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSI1	NM_002442.4 link	c.*999A>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000257552.7	NP_002433.1	O43347

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSI1	ENST00000257552.7 link	c.*999A>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_002442.4	ENSP00000257552.2		O43347

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62628

AN:

151676

Hom.:

14393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.502

AC:

569

AN:

1134

Hom.:

156

Cov.:

AF XY:

0.492

AC XY:

394

AN XY:

800

show subpopulations

African (AFR)

AF:

0.278

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

0.567

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.514

AC:

224

AN:

436

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.491

AC:

284

AN:

578

Other (OTH)

AF:

0.441

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.413

AC:

62659

AN:

151794

Hom.:

14409

Cov.:

AF XY:

0.413

AC XY:

30611

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.204

AC:

8439

AN:

41434

American (AMR)

AF:

0.442

AC:

6747

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1540

AN:

3472

East Asian (EAS)

AF:

0.365

AC:

1862

AN:

5104

South Asian (SAS)

AF:

0.553

AC:

2663

AN:

4816

European-Finnish (FIN)

AF:

0.506

AC:

5326

AN:

10522

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34297

AN:

67872

Other (OTH)

AF:

0.489

AC:

1028

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1799

3598

5397

7196

8995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.480

Hom.:

29510

Bravo

AF:

0.399

Asia WGS

AF:

0.491

AC:

1701

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.2

(source)

DANN

Benign

0.46

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over