Variant 19-757465-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000215582.8(MISP):c.519C>T(p.Pro173Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000662 in 1,592,952 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 8 hom. )

Consequence

MISP
ENST00000215582.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.20

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 19-757465-C-T is Benign according to our data. Variant chr19-757465-C-T is described in ClinVar as [Benign]. Clinvar id is 731848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00066 (951/1440946) while in subpopulation EAS AF= 0.0204 (794/38850). AF 95% confidence interval is 0.0193. There are 8 homozygotes in gnomad4_exome. There are 471 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MISP	NM_173481.4 linkuse as main transcript	c.519C>T	p.Pro173Pro	synonymous_variant	2/5	ENST00000215582.8	NP_775752.1	Q8IVT2
MISP	XM_011527685.3 linkuse as main transcript	c.519C>T	p.Pro173Pro	synonymous_variant	2/5		XP_011525987.1	Q8IVT2
MISP	XM_011527686.3 linkuse as main transcript	c.519C>T	p.Pro173Pro	synonymous_variant	2/5		XP_011525988.1	Q8IVT2
MISP	NR_135168.2 linkuse as main transcript	n.61-2444C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MISP	ENST00000215582.8 linkuse as main transcript	c.519C>T	p.Pro173Pro	synonymous_variant	2/5	1	NM_173481.4	ENSP00000215582.4		Q8IVT2

Frequencies

GnomAD3 genomes

AF:

0.000678

AC:

103

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00139

AC:

290

AN:

208312

Hom.:

AF XY:

0.00125

AC XY:

141

AN XY:

112554

show subpopulations

Gnomad AFR exome

AF:

0.0000797

Gnomad AMR exome

AF:

0.000105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0174

Gnomad SAS exome

AF:

0.000402

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.000568

GnomAD4 exome

AF:

0.000660

AC:

951

AN:

1440946

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

471

AN XY:

715036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000753

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.0204

Gnomad4 SAS exome

AF:

0.000597

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000508

Gnomad4 OTH exome

AF:

0.000754

GnomAD4 genome

AF:

0.000678

AC:

103

AN:

152006

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000710

Asia WGS

AF:

0.00693

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	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.49

DANN

Benign

0.71

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