Variant chr19-757321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000215582.8(MISP):c.375C>T(p.Arg125Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,613,988 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0085 ( 70 hom. )

Consequence

MISP
ENST00000215582.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.51

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 19-757321-C-T is Benign according to our data. Variant chr19-757321-C-T is described in ClinVar as [Benign]. Clinvar id is 779178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MISP	NM_173481.4 linkuse as main transcript	c.375C>T	p.Arg125Arg	synonymous_variant	2/5	ENST00000215582.8	NP_775752.1	Q8IVT2
MISP	XM_011527685.3 linkuse as main transcript	c.375C>T	p.Arg125Arg	synonymous_variant	2/5		XP_011525987.1	Q8IVT2
MISP	XM_011527686.3 linkuse as main transcript	c.375C>T	p.Arg125Arg	synonymous_variant	2/5		XP_011525988.1	Q8IVT2
MISP	NR_135168.2 linkuse as main transcript	n.61-2588C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MISP	ENST00000215582.8 linkuse as main transcript	c.375C>T	p.Arg125Arg	synonymous_variant	2/5	1	NM_173481.4	ENSP00000215582.4		Q8IVT2

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

953

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00614

AC:

1532

AN:

249690

Hom.:

AF XY:

0.00600

AC XY:

812

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00607

GnomAD4 exome

AF:

0.00852

AC:

12454

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00827

AC XY:

6016

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00349

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00739

GnomAD4 genome

AF:

0.00626

AC:

953

AN:

152320

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00216

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00664

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.0109

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	Nov 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.3

DANN

Benign

0.54

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