Variant 19-757037-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000215582.8(MISP):c.91T>C(p.Tyr31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,607,886 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 81 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 61 hom. )

Consequence

MISP
ENST00000215582.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.485

Variant links:

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]

MISP links:

MISP (HGNC:):

MISP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023950934).

BP6

Variant 19-757037-T-C is Benign according to our data. Variant chr19-757037-T-C is described in ClinVar as [Benign]. Clinvar id is 769445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MISP	NM_173481.4 linkuse as main transcript	c.91T>C	p.Tyr31His	missense_variant	2/5	ENST00000215582.8	NP_775752.1	Q8IVT2
MISP	XM_011527685.3 linkuse as main transcript	c.91T>C	p.Tyr31His	missense_variant	2/5		XP_011525987.1	Q8IVT2
MISP	XM_011527686.3 linkuse as main transcript	c.91T>C	p.Tyr31His	missense_variant	2/5		XP_011525988.1	Q8IVT2
MISP	NR_135168.2 linkuse as main transcript	n.61-2872T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MISP	ENST00000215582.8 linkuse as main transcript	c.91T>C	p.Tyr31His	missense_variant	2/5	1	NM_173481.4	ENSP00000215582.4		Q8IVT2

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2675

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00680

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:

0.000426

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.00469

AC:

1103

AN:

235350

Hom.:

AF XY:

0.00345

AC XY:

442

AN XY:

128262

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00225

GnomAD4 exome

AF:

0.00188

AC:

2736

AN:

1455596

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1227

AN XY:

723894

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.00417

Gnomad4 ASJ exome

AF:

0.0000769

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000819

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.0177

AC:

2703

AN:

152290

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1244

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0607

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00629

Hom.:

Bravo

AF:

0.0205

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0577

AC:

254

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00526

AC:

638

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.30

Sift

Uncertain

0.021

Sift4G

Benign

0.38

Polyphen

0.95

Vest4

0.12

MVP

0.32

MPC

0.20

ClinPred

0.0069

GERP RS

-1.7

Varity_R

0.067

gMVP

0.11

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

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