17-57676999-G-T

Variant names:

• chr17-57676999-G-T
• rs759553636
• NM_138962.4:c.958G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_138962.4(MSI2):​c.958G>T​(p.Ala320Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,612,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A320T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: MSI2 NM_138962.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3214957).
• BS2: High AC in GnomAdExome4 at 36 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.958G>T	p.Ala320Ser	missense	Exon 13 of 14	NP_620412.1	Q96DH6-1
	MSI2	NM_001322250.2		c.946G>T	p.Ala316Ser	missense	Exon 13 of 14	NP_001309179.1	B4DHE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSI2	ENST00000284073.7	TSL:1 MANE Select	c.958G>T	p.Ala320Ser	missense	Exon 13 of 14	ENSP00000284073.2	Q96DH6-1
	MSI2	ENST00000902711.1		c.1042G>T	p.Ala348Ser	missense	Exon 14 of 15	ENSP00000572770.1
	MSI2	ENST00000902712.1		c.1000G>T	p.Ala334Ser	missense	Exon 13 of 14	ENSP00000572771.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251492 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.0000247 AC: 36 AN: 1460418 Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18 AN XY: 726646

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.000604 AC: 27 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110666

Other (OTH) AF: 0.0000331 AC: 2 AN: 60354

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000988 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.0052	T
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.8	L
PhyloP100		9.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.014	D
Sift4G	Benign	0.20	T
Polyphen		0.98	D
Vest4		0.64
MutPred		0.34		Gain of glycosylation at A320 (P = 0.0035)
MVP		0.79
MPC		1.8
ClinPred		0.28	T
GERP RS		4.9
Varity_R		0.27
gMVP		0.78
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs759553636; hg19: chr17-55754360;