chr19-8861016-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001414686.1(MUC16):c.43548G>A(p.Val14516Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
MUC16
NM_001414686.1 synonymous
NM_001414686.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.47
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 19-8861016-C-T is Benign according to our data. Variant chr19-8861016-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045941.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-3.47 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MUC16 | NM_001414686.1 | c.43548G>A | p.Val14516Val | synonymous_variant | 88/94 | NP_001401615.1 | ||
| MUC16 | NM_001401501.2 | c.43122G>A | p.Val14374Val | synonymous_variant | 87/93 | NP_001388430.1 | ||
| MUC16 | NM_001414687.1 | c.43002G>A | p.Val14334Val | synonymous_variant | 84/90 | NP_001401616.1 | ||
| MUC16 | NM_024690.2 | c.42900G>A | p.Val14300Val | synonymous_variant | 78/84 | NP_078966.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MUC16 | ENST00000710609.1 | c.43020G>A | p.Val14340Val | synonymous_variant | 81/87 | ENSP00000518375.1 | ||||
| MUC16 | ENST00000397910.8 | c.42900G>A | p.Val14300Val | synonymous_variant | 78/84 | 5 | ENSP00000381008.2 | |||
| MUC16 | ENST00000710610.1 | c.33726G>A | p.Val11242Val | synonymous_variant | 80/86 | ENSP00000518376.1 |
Frequencies
GnomAD3 genomes 0.000138 AC: 21AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000884 AC: 22AN: 248954Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135074
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GnomAD4 exome AF: 0.000132 AC: 193AN: 1461468Hom.: 0 Cov.: 30 AF XY: 0.000143 AC XY: 104AN XY: 727008
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GnomAD4 genome 0.000138 AC: 21AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
MUC16-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at