Genetic Variant MUC6:p.Pro1724TrpfsTer10 (chr11-1017608-ACTGGTGGTCACTGTCATTGGTGG-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.5170_5192delCCACCAATGACAGTGACCACCAG(p.Pro1724TrpfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. 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 0.0010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000036 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC6
NM_005961.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

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:

Genome browser will be placed here

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.5170_5192delCCACCAATGACAGTGACCACCAG	p.Pro1724TrpfsTer10	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.5170_5192delCCACCAATGACAGTGACCACCAG	p.Pro1724TrpfsTer10	frameshift	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

AN:

58646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000302

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000840

Gnomad SAS

AF:

0.000988

Gnomad FIN

AF:

0.00214

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000363

AC:

AN:

1210972

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

602306

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

28676

American (AMR)

AF:

0.0000286

AC:

AN:

34952

Ashkenazi Jewish (ASJ)

AF:

0.000141

AC:

AN:

21314

East Asian (EAS)

AF:

0.0000304

AC:

AN:

32856

South Asian (SAS)

AF:

0.00

AC:

AN:

68326

European-Finnish (FIN)

AF:

0.000115

AC:

AN:

43490

Middle Eastern (MID)

AF:

0.000206

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.0000335

AC:

AN:

926122

Other (OTH)

AF:

0.0000397

AC:

AN:

50380

⚠️ 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: 0.225

Heterozygous variant carriers

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:

0.00101

AC:

AN:

58704

Hom.:

Cov.:

AF XY:

0.000893

AC XY:

AN XY:

29114

show subpopulations

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

African (AFR)

AF:

0.00112

AC:

AN:

16072

American (AMR)

AF:

0.000302

AC:

AN:

6618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1290

East Asian (EAS)

AF:

0.000844

AC:

AN:

2370

South Asian (SAS)

AF:

0.000992

AC:

AN:

2016

European-Finnish (FIN)

AF:

0.00214

AC:

AN:

4664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

24406

Other (OTH)

AF:

0.00

AC:

AN:

848

⚠️ 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: 0.268

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:

0.00246

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=90/110

disease causing (fs/PTC)

(source)

Splicing

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