rs2033568720

Variant names:

• chr19-757342-C-A
• rs2033568720
• NM_173481.4:c.396C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-757342-C-A
• chr19-757342-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173481.4(MISP):​c.396C>A​(p.Asp132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MISP NM_173481.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.54
• Publications: 0 publications found

Genes affected

MISP (HGNC:27000): (mitotic spindle positioning) The protein encoded by this gene is an actin-bundling protein involved in determining cell morphology and mitotic progression. The encoded protein is required for the proper positioning of the mitotic spindle. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03835067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173481.4. 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
	MISP	NM_173481.4	MANE Select	c.396C>A	p.Asp132Glu	missense	Exon 2 of 5	NP_775752.1	Q8IVT2
	MISP	NR_135168.2		n.61-2567C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MISP	ENST00000215582.8	TSL:1 MANE Select	c.396C>A	p.Asp132Glu	missense	Exon 2 of 5	ENSP00000215582.4	Q8IVT2
	MISP	ENST00000871265.1		c.396C>A	p.Asp132Glu	missense	Exon 2 of 5	ENSP00000541324.1
	MISP	ENST00000871267.1		c.396C>A	p.Asp132Glu	missense	Exon 2 of 5	ENSP00000541326.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.24
DANN	Benign	0.81
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.056
Sift	Benign	0.99	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.27		Gain of disorder (P = 0.2133)
MVP		0.21
MPC		0.036
ClinPred		0.058	T
GERP RS		-1.8
Varity_R		0.034
gMVP		0.022
Mutation Taster		=100/0	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: rs2033568720; hg19: chr19-757342;