rs753289768

Variant names:

• chr17-57257477-G-A
• rs753289768
• NM_138962.4:c.115G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-57257477-G-A
• chr17-57257477-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_138962.4(MSI2):​c.115G>A​(p.Asp39Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,429,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSI2 NM_138962.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.79
• Publications: 1 publications found

Genes affected

MSI2 (HGNC:18585): (musashi RNA binding protein 2) This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138962.4. 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
	MSI2	NM_138962.4	MANE Select	c.115G>A	p.Asp39Asn	missense	Exon 3 of 14	NP_620412.1	Q96DH6-1
	MSI2	NM_001322250.2		c.49G>A	p.Asp17Asn	missense	Exon 3 of 14	NP_001309179.1	B4DHE8
	MSI2	NM_001322251.2		c.115G>A	p.Asp39Asn	missense	Exon 3 of 11	NP_001309180.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI2	ENST00000284073.7	TSL:1 MANE Select	c.115G>A	p.Asp39Asn	missense	Exon 3 of 14	ENSP00000284073.2	Q96DH6-1
	MSI2	ENST00000902711.1		c.115G>A	p.Asp39Asn	missense	Exon 3 of 15	ENSP00000572770.1
	MSI2	ENST00000902712.1		c.115G>A	p.Asp39Asn	missense	Exon 3 of 14	ENSP00000572771.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149896 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250258 AF XY: 0.00000738

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 24 AN: 1429254 Hom.: 0 Cov.: 28 AF XY: 0.0000112 AC XY: 8 AN XY: 712912

African (AFR) AF: 0.00 AC: 0 AN: 32592

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.0000203 AC: 22 AN: 1083576

Other (OTH) AF: 0.0000169 AC: 1 AN: 59252

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149896 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73054

African (AFR) AF: 0.00 AC: 0 AN: 40302

American (AMR) AF: 0.00 AC: 0 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67682

Other (OTH) AF: 0.00 AC: 0 AN: 2044

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	Benign	0.29
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.038	D
MutationAssessor	Benign	0.63	N
PhyloP100		8.8
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.39
Sift	Benign	0.15	T
Sift4G	Uncertain	0.041	D
Polyphen		0.46	P
Vest4		0.34
MutPred		0.47		Loss of ubiquitination at K43 (P = 0.074)
MVP		0.82
MPC		1.0
ClinPred		0.60	D
GERP RS		2.6
PromoterAI		0.012	Neutral
Varity_R		0.45
gMVP		0.79
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs753289768; hg19: chr17-55334838;