Variant rs1057147 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005823.6(MSLN):c.*69G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,476,340 control chromosomes in the GnomAD database, including 31,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3415 hom., cov: 32)

Exomes 𝑓: 0.21 ( 28566 hom. )

Consequence

MSLN
NM_005823.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

MSLN (HGNC:7371): (mesothelin) This gene encodes a preproprotein that is proteolytically processed to generate two protein products, megakaryocyte potentiating factor and mesothelin. Megakaryocyte potentiating factor functions as a cytokine that can stimulate colony formation of bone marrow megakaryocytes. Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface protein that may function as a cell adhesion protein. This protein is overexpressed in epithelial mesotheliomas, ovarian cancers and in specific squamous cell carcinomas. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

MSLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043660104).

BP6

Variant 16-768802-G-A is Benign according to our data. Variant chr16-768802-G-A is described in ClinVar as [Benign]. Clinvar id is 1232817.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MSLN	NM_005823.6 linkuse as main transcript	c.*69G>A	3_prime_UTR_variant	18/18	ENST00000545450.7
MSLN	NM_001177355.3 linkuse as main transcript	c.*69G>A	3_prime_UTR_variant	18/18
MSLN	NM_013404.4 linkuse as main transcript	c.*69G>A	3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSLN	ENST00000545450.7 linkuse as main transcript	c.*69G>A		3_prime_UTR_variant	18/18	1	NM_005823.6	P2	Q13421-3

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31905

AN:

151856

Hom.:

3414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.210

AC:

47489

AN:

226626

Hom.:

4911

AF XY:

0.206

AC XY:

25669

AN XY:

124682

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.206

AC:

273063

AN:

1324366

Hom.:

28566

Cov.:

AF XY:

0.206

AC XY:

136767

AN XY:

664832

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.210

AC:

31919

AN:

151974

Hom.:

3415

Cov.:

AF XY:

0.207

AC XY:

15344

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.208

Hom.:

1994

Bravo

AF:

0.215

TwinsUK

AF:

0.210

AC:

779

ALSPAC

AF:

0.205

AC:

791

ExAC

AF:

0.203

AC:

24257

Asia WGS

AF:

0.237

AC:

826

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 25436799) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.9

DANN

Benign

0.66

DEOGEN2

Benign

0.0078

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0044

MutationTaster

Benign

1.0

P;P;P;P;P;P

PROVEAN

Benign

0.040

Sift

Benign

1.0

GERP RS

-2.7

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