12-120342128-T-G

Position:

• chr12-120342128-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MSI1	NM_002442.4	c.*999A>C		3_prime_UTR_variant	15/15	ENST00000257552.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSI1	ENST00000257552.7	c.*999A>C		3_prime_UTR_variant	15/15	1	NM_002442.4	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62628 AN: 151676 Hom.: 14393 Cov.: 30

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.: 0 AF XY: 0.492 AC XY: 394 AN XY: 800

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.413 AC: 62659 AN: 151794 Hom.: 14409 Cov.: 30 AF XY: 0.413 AC XY: 30611 AN XY: 74164

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.489

Alfa AF: 0.490 Hom.: 23928

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
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs2522137; hg19: chr12-120779931; COSMIC: COSV57455242; COSMIC: COSV57455242;