Variant 16-765202-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 NM_005823.6(MSLN):c.603C>T(p.Ala201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,591,668 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 45 hom., cov: 34)

Exomes 𝑓: 0.0029 ( 58 hom. )

Consequence

MSLN
NM_005823.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-765202-C-T is Benign according to our data. Variant chr16-765202-C-T is described in ClinVar as [Benign]. Clinvar id is 789826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2244/152352) while in subpopulation AFR AF= 0.0445 (1848/41574). AF 95% confidence interval is 0.0428. There are 45 homozygotes in gnomad4. There are 1037 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MSLN	NM_005823.6 linkuse as main transcript	c.603C>T	p.Ala201=	synonymous_variant	9/18	ENST00000545450.7	NP_005814.2
MSLN	NM_013404.4 linkuse as main transcript	c.603C>T	p.Ala201=	synonymous_variant	8/17		NP_037536.2
MSLN	NM_001177355.3 linkuse as main transcript	c.603C>T	p.Ala201=	synonymous_variant	9/18		NP_001170826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSLN	ENST00000545450.7 linkuse as main transcript	c.603C>T	p.Ala201=	synonymous_variant	9/18	1	NM_005823.6	ENSP00000442965	P2	Q13421-3

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2239

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00588

AC:

1219

AN:

207176

Hom.:

AF XY:

0.00491

AC XY:

562

AN XY:

114418

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.00743

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.000121

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.00804

GnomAD4 exome

AF:

0.00292

AC:

4196

AN:

1439316

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

1995

AN XY:

715598

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00696

GnomAD4 genome

AF:

0.0147

AC:

2244

AN:

152352

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1037

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0445

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00730

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00433

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 09, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.35

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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