NM_001414686.1:c.43559T>G

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001414686.1(MUC16):c.43559T>G(p.Val14520Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,524 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MUC16
NM_001414686.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.15

Variant links:

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]

MUC16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 19-8861005-A-C is Benign according to our data. Variant chr19-8861005-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649215.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
MUC16	NM_001414686.1 link	c.43559T>G	p.Val14520Gly	missense_variant	Exon 88 of 94	NP_001401615.1
MUC16	NM_001401501.2 link	c.43133T>G	p.Val14378Gly	missense_variant	Exon 87 of 93	NP_001388430.1
MUC16	NM_001414687.1 link	c.43013T>G	p.Val14338Gly	missense_variant	Exon 84 of 90	NP_001401616.1
MUC16	NM_024690.2 link	c.42911T>G	p.Val14304Gly	missense_variant	Exon 78 of 84	NP_078966.2	Q8WXI7B3KY81

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
MUC16	ENST00000710609.1 link	c.43031T>G	p.Val14344Gly	missense_variant	Exon 81 of 87		ENSP00000518375.1
MUC16	ENST00000397910.8 link	c.42911T>G	p.Val14304Gly	missense_variant	Exon 78 of 84	5	ENSP00000381008.2	Q8WXI7
MUC16	ENST00000710610.1 link	c.33737T>G	p.Val11246Gly	missense_variant	Exon 80 of 86		ENSP00000518376.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

248838

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MUC16: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.30

M_CAP

Benign

0.052

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.53

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.23

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0010

Vest4

0.34

MVP

0.36

ClinPred

0.89

GERP RS

4.0

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over