rs8109594

Positions:

• chr19-9035796-G-A
• chr19-9035796-G-C

Variant summary

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

The NM_001414686.1(MUC16):​c.355C>T​(p.Pro119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,008 control chromosomes in the GnomAD database, including 6,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6215 hom., cov: 31)
• Consequence: MUC16 NM_001414686.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

Genes affected

MUC16 (HGNC:15582): (mucin 16, cell surface associated) This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes. [provided by RefSeq, May 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC16	NM_001414686.1	c.355C>T	p.Pro119Ser	missense_variant	2/94		NP_001401615.1
		n.9035796G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40450 AN: 151888 Hom.: 6206 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40494 AN: 152008 Hom.: 6215 Cov.: 31 AF XY: 0.268 AC XY: 19917 AN XY: 74298

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.244

Alfa AF: 0.201 Hom.: 6622

Bravo AF: 0.262

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8109594; hg19: chr19-9146472;