rs57272256

Positions:

• chr16-768807-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005823.6(MSLN):​c.*74C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,416,358 control chromosomes in the GnomAD database, including 2,226 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (989 hom., cov: 32)
  • Exomes 𝑓: 0.022 (1237 hom.)
• Consequence: MSLN NM_005823.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSLN	NM_005823.6	c.*74C>T		3_prime_UTR_variant	18/18	ENST00000545450.7	NP_005814.2
MSLN	NM_013404.4	c.*74C>T		3_prime_UTR_variant	17/17		NP_037536.2
MSLN	NM_001177355.3	c.*74C>T		3_prime_UTR_variant	18/18		NP_001170826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSLN	ENST00000545450.7	c.*74C>T		3_prime_UTR_variant	18/18	1	NM_005823.6	ENSP00000442965.2

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10851 AN: 152018 Hom.: 984 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0636

GnomAD3 exomes AF: 0.0398 AC: 8793 AN: 221164 Hom.: 487 AF XY: 0.0380 AC XY: 4631 AN XY: 121950

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0504

Gnomad EAS exome AF: 0.0405

Gnomad SAS exome AF: 0.0788

Gnomad FIN exome AF: 0.00557

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0318

GnomAD4 exome AF: 0.0218 AC: 27572 AN: 1264222 Hom.: 1237 Cov.: 19 AF XY: 0.0232 AC XY: 14795 AN XY: 637154

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.0519

Gnomad4 EAS exome AF: 0.0264

Gnomad4 SAS exome AF: 0.0761

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.00956

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.0715 AC: 10878 AN: 152136 Hom.: 989 Cov.: 32 AF XY: 0.0705 AC XY: 5240 AN XY: 74378

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0431 Hom.: 94

Bravo AF: 0.0796

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs57272256; hg19: chr16-818807;