rs57272256

Variant names:

• chr16-768807-C-T
• rs57272256
• NM_005823.6:c.*74C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005823.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSLN	NM_005823.6	MANE Select	c.*74C>T		3_prime_UTR	Exon 18 of 18	NP_005814.2
	MSLN	NM_013404.4		c.*74C>T		3_prime_UTR	Exon 17 of 17	NP_037536.2
	MSLN	NM_001177355.3		c.*74C>T		3_prime_UTR	Exon 18 of 18	NP_001170826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSLN	ENST00000545450.7	TSL:1 MANE Select	c.*74C>T		3_prime_UTR	Exon 18 of 18	ENSP00000442965.2
	MSLN	ENST00000563941.5	TSL:1	c.*74C>T		3_prime_UTR	Exon 18 of 18	ENSP00000456008.1
	MSLN	ENST00000566549.5	TSL:1	c.*74C>T		3_prime_UTR	Exon 17 of 17	ENSP00000456702.1

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

GnomAD2 exomes AF: 0.0398 AC: 8793 AN: 221164 AF XY: 0.0380

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 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

African (AFR) AF: 0.215 AC: 6359 AN: 29576

American (AMR) AF: 0.0227 AC: 965 AN: 42506

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1269 AN: 24446

East Asian (EAS) AF: 0.0264 AC: 1010 AN: 38306

South Asian (SAS) AF: 0.0761 AC: 6248 AN: 82088

European-Finnish (FIN) AF: 0.00591 AC: 243 AN: 41096

Middle Eastern (MID) AF: 0.0785 AC: 425 AN: 5412

European-Non Finnish (NFE) AF: 0.00956 AC: 9055 AN: 947056

Other (OTH) AF: 0.0372 AC: 1998 AN: 53736

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

African (AFR) AF: 0.209 AC: 8650 AN: 41484

American (AMR) AF: 0.0329 AC: 504 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.0345 AC: 178 AN: 5166

South Asian (SAS) AF: 0.0758 AC: 365 AN: 4814

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 759 AN: 67966

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.65
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57272256; hg19: chr16-818807;