Genetic Variant MUC6:p.Arg1779* (chr11-1017466-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005961.3(MUC6):c.5335A>T(p.Arg1779*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,134,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.037 ( 0 hom., cov: 119)

Exomes 𝑓: 0.0012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC6
NM_005961.3 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: -2.47

Variant links:

Genes affected

MUC6 (HGNC:7517): (mucin 6, oligomeric mucus/gel-forming) This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. [provided by RefSeq, Dec 2016]

MUC6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3 link	c.5335A>T	p.Arg1779*	stop_gained	Exon 31 of 33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7 link	c.5335A>T	p.Arg1779*	stop_gained	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2		Q6W4X9

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

3720

AN:

101610

Hom.:

Cov.:

119

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.0498

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0290

Gnomad EAS

AF:

0.0244

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.0549

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0388

GnomAD4 exome

AF:

0.00123

AC:

1391

AN:

1134348

Hom.:

Cov.:

306

AF XY:

0.00130

AC XY:

718

AN XY:

551408

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

AC:

AN:

25458

Gnomad4 AMR exome

AF:

0.00395

AC:

AN:

24570

Gnomad4 ASJ exome

AF:

0.00120

AC:

AN:

17438

Gnomad4 EAS exome

AF:

0.00129

AC:

AN:

23988

Gnomad4 SAS exome

AF:

0.00176

AC:

105

AN:

59586

Gnomad4 FIN exome

AF:

0.00780

AC:

210

AN:

26914

Gnomad4 NFE exome

AF:

0.000905

AC:

822

AN:

908248

Gnomad4 Remaining exome

AF:

0.00160

AC:

AN:

44340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Heterozygous variant carriers

287

574

862

1149

1436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0365

AC:

3713

AN:

101694

Hom.:

Cov.:

119

AF XY:

0.0383

AC XY:

1896

AN XY:

49502

show subpopulations

Gnomad4 AFR

AF:

0.0272

AC:

0.0271911

AN:

0.0271911

Gnomad4 AMR

AF:

0.0472

AC:

0.047155

AN:

0.047155

Gnomad4 ASJ

AF:

0.0290

AC:

0.0289728

AN:

0.0289728

Gnomad4 EAS

AF:

0.0241

AC:

0.02414

AN:

0.02414

Gnomad4 SAS

AF:

0.0368

AC:

0.0367787

AN:

0.0367787

Gnomad4 FIN

AF:

0.0514

AC:

0.0514113

AN:

0.0514113

Gnomad4 NFE

AF:

0.0389

AC:

0.0389039

AN:

0.0389039

Gnomad4 OTH

AF:

0.0377

AC:

0.0377493

AN:

0.0377493

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Heterozygous variant carriers

469

939

1408

1878

2347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

104

156

208

260

<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:

0.00

Hom.:

ExAC

AF:

0.0307

AC:

3595

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Small cell lung carcinoma

Pathogenic:1

Jun 15, 2021

Arun Kumar Laboratory, Indian Institute of Science

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Lung cancer

Pathogenic:1

Jun 15, 2021

Arun Kumar Laboratory, Indian Institute of Science

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Benign

0.97

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.036

Vest4

0.11

GERP RS

0.018

Mutation Taster

=92/108

disease causing (fs/PTC)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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