Variant chr12-120357901-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002442.4(MSI1):c.452-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,614,166 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 20 hom. )

Consequence

MSI1
NM_002442.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008791

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0530

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-120357901-A-G is Benign according to our data. Variant chr12-120357901-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 721285.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSI1	NM_002442.4 linkuse as main transcript	c.452-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000257552.7	NP_002433.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MSI1	ENST00000257552.7 linkuse as main transcript	c.452-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002442.4	ENSP00000257552	P1
MSI1	ENST00000546985.1 linkuse as main transcript	c.247-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000446710
MSI1	ENST00000546622.1 linkuse as main transcript	n.165-3T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00247

AC:

620

AN:

251438

Hom.:

AF XY:

0.00260

AC XY:

353

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00231

AC:

3374

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1775

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00691

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.00199

GnomAD4 genome

AF:

0.00207

AC:

316

AN:

152348

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

159

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00640

Gnomad4 NFE

AF:

0.00329

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00122

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.0

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000088

dbscSNV1_RF

Benign

0.0020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over