chr19-8868536-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6
The NM_001414686.1(MUC16):c.42802+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000216 in 1,613,702 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
MUC16
NM_001414686.1 splice_region, intron
NM_001414686.1 splice_region, intron
Scores
2
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 3.69
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
Variant 19-8868536-C-T is Benign according to our data. Variant chr19-8868536-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051705.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MUC16 | NM_001414686.1 | c.42802+5G>A | splice_region_variant, intron_variant | Intron 81 of 93 | NP_001401615.1 | |||
| MUC16 | NM_001401501.2 | c.42376+5G>A | splice_region_variant, intron_variant | Intron 80 of 92 | NP_001388430.1 | |||
| MUC16 | NM_001414687.1 | c.42256+5G>A | splice_region_variant, intron_variant | Intron 77 of 89 | NP_001401616.1 | |||
| MUC16 | NM_024690.2 | c.42154+5G>A | splice_region_variant, intron_variant | Intron 71 of 83 | NP_078966.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MUC16 | ENST00000710609.1 | c.42274+5G>A | splice_region_variant, intron_variant | Intron 74 of 86 | ENSP00000518375.1 | |||||
| MUC16 | ENST00000397910.8 | c.42154+5G>A | splice_region_variant, intron_variant | Intron 71 of 83 | 5 | ENSP00000381008.2 | ||||
| MUC16 | ENST00000710610.1 | c.32980+5G>A | splice_region_variant, intron_variant | Intron 73 of 85 | ENSP00000518376.1 |
Frequencies
GnomAD3 genomes 0.000224 AC: 34AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000398 AC: 99AN: 248980Hom.: 0 AF XY: 0.000392 AC XY: 53AN XY: 135048
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GnomAD4 exome AF: 0.000216 AC: 315AN: 1461470Hom.: 1 Cov.: 31 AF XY: 0.000198 AC XY: 144AN XY: 727014
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GnomAD4 genome 0.000223 AC: 34AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74422
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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
Mar 31, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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dbscSNV1_ADA
Pathogenic
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Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at