19-8865686-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_001401501.2(MUC16):c.42688G>A(p.Gly14230Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,598,282 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00067 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00053 ( 3 hom. )

Consequence

MUC16
NM_001401501.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.877

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073460042).

BP6

Variant 19-8865686-C-T is Benign according to our data. Variant chr19-8865686-C-T is described in ClinVar as Benign. ClinVar VariationId is 3040472.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001401501.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC16	NM_001401501.2	MANE Select	c.42688G>A	p.Gly14230Arg	missense	Exon 84 of 93	NP_001388430.1	A0AAG2UXK0
MUC16	NM_001414686.1		c.43114G>A	p.Gly14372Arg	missense	Exon 85 of 94	NP_001401615.1
MUC16	NM_001414687.1		c.42568G>A	p.Gly14190Arg	missense	Exon 81 of 90	NP_001401616.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC16	ENST00000397910.8	TSL:5	c.42466G>A	p.Gly14156Arg	missense	Exon 75 of 84	ENSP00000381008.2	Q8WXI7
MUC16	ENST00000711672.1		c.42652G>A	p.Gly14218Arg	missense	Exon 79 of 88	ENSP00000518832.1	A0AAA9YHI4
MUC16	ENST00000710609.1		c.42586G>A	p.Gly14196Arg	missense	Exon 78 of 87	ENSP00000518375.1	A0AA34QW05

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00124

AC:

288

AN:

232844

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00911

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.000358

GnomAD4 exome

AF:

0.000535

AC:

773

AN:

1446064

Hom.:

Cov.:

AF XY:

0.000669

AC XY:

481

AN XY:

719172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32364

American (AMR)

AF:

0.0000255

AC:

AN:

39194

Ashkenazi Jewish (ASJ)

AF:

0.0000396

AC:

AN:

25236

East Asian (EAS)

AF:

0.00937

AC:

371

AN:

39612

South Asian (SAS)

AF:

0.00364

AC:

305

AN:

83820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.000705

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0000524

AC:

AN:

1107236

Other (OTH)

AF:

0.000553

AC:

AN:

59706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152218

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.000262

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0114

AC:

AN:

5158

South Asian (SAS)

AF:

0.00373

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68020

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000875

Hom.:

Bravo

AF:

0.000366

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00106

AC:

128

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MUC16-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.78

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.96

PhyloP100

-0.88

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.040

REVEL

Benign

0.13

Sift

Benign

0.098

Sift4G

Benign

0.68

Vest4

0.16

MVP

0.21

ClinPred

0.048

GERP RS

0.43

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over