dbSNP rs1856666641: MUC6:p.Ser1734ProfsTer69 (chr11-1017463-TTCTGGTGCCTGTACTGGTGTGGTTGGGGGTGATGCTGGTGGTAGAAGTTGAGGTGACTTCAGGATGGTGTGTGGAGGAAGTGTGTGAATGTAGGGATGTAGAGGTTTTGGCCGTGCTAAATGAGCTTCGGGATTGGCTG-T) – 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.5199_5337del(p.Ser1734ProfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,405,114 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 118)

Exomes 𝑓: 0.00018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC6
NM_005961.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

0 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005961.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC6	NM_005961.3	MANE Select	c.5199_5337del	p.Ser1734ProfsTer69	frameshift	Exon 31 of 33	NP_005952.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC6	ENST00000421673.7	TSL:5 MANE Select	c.5199_5337del	p.Ser1734ProfsTer69	frameshift	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

487

AN:

139470

Hom.:

Cov.:

118

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00353

Gnomad AMR

AF:

0.00422

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00107

Gnomad SAS

AF:

0.000447

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00340

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.00686

GnomAD2 exomes

AF:

0.00

AC:

AN:

249202

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000181

AC:

254

AN:

1405114

Hom.:

AF XY:

0.000189

AC XY:

132

AN XY:

698454

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000309

AC:

AN:

32390

American (AMR)

AF:

0.000167

AC:

AN:

42012

Ashkenazi Jewish (ASJ)

AF:

0.000164

AC:

AN:

24412

East Asian (EAS)

AF:

0.000273

AC:

AN:

36584

South Asian (SAS)

AF:

0.000193

AC:

AN:

82826

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

47444

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.000140

AC:

151

AN:

1076948

Other (OTH)

AF:

0.000245

AC:

AN:

57192

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.234

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00352

AC:

491

AN:

139592

Hom.:

Cov.:

118

AF XY:

0.00360

AC XY:

247

AN XY:

68532

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00271

AC:

105

AN:

38698

American (AMR)

AF:

0.00422

AC:

AN:

13992

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3114

East Asian (EAS)

AF:

0.00107

AC:

AN:

4672

South Asian (SAS)

AF:

0.000447

AC:

AN:

4474

European-Finnish (FIN)

AF:

0.00661

AC:

AN:

9980

Middle Eastern (MID)

AF:

0.00360

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00365

AC:

225

AN:

61620

Other (OTH)

AF:

0.00836

AC:

AN:

1914

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

170

256

341

426

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:

0.0659

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.027

Mutation Taster

=89/111

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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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