dbSNP rs111749447: MUC6:p.Thr1544del (chr11-1018167-ATCG-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PM4_SupportingBP6_Moderate

The NM_005961.3(MUC6):c.4631_4633delCGA(p.Thr1544del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,315,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC6
NM_005961.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0860

Publications

3 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 1 ACMG points.

PM2

Variant has high frequency in the AMR (0.0103) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).

PM4

Nonframeshift variant in NON repetitive region in NM_005961.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 11-1018167-ATCG-A is Benign according to our data. Variant chr11-1018167-ATCG-A is described in ClinVar as Benign. ClinVar VariationId is 403202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3 link	c.4631_4633delCGA	p.Thr1544del	disruptive_inframe_deletion	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.4631_4633delCGA	p.Thr1544del	disruptive_inframe_deletion	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

105212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000355

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000318

Gnomad SAS

AF:

0.000346

Gnomad FIN

AF:

0.000141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000992

Gnomad OTH

AF:

0.000680

GnomAD2 exomes

AF:

0.00195

AC:

200

AN:

102664

AF XY:

0.00241

show subpopulations

Gnomad AFR exome

AF:

0.000183

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00364

Gnomad EAS exome

AF:

0.00534

Gnomad FIN exome

AF:

0.000246

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000894

GnomAD4 exome

AF:

0.00195

AC:

2565

AN:

1315560

Hom.:

AF XY:

0.00233

AC XY:

1528

AN XY:

655462

show subpopulations

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

African (AFR)

AF:

0.00295

AC:

AN:

29880

American (AMR)

AF:

0.0112

AC:

422

AN:

37800

Ashkenazi Jewish (ASJ)

AF:

0.00792

AC:

184

AN:

23242

East Asian (EAS)

AF:

0.000262

AC:

AN:

38236

South Asian (SAS)

AF:

0.00977

AC:

736

AN:

75356

European-Finnish (FIN)

AF:

0.00222

AC:

113

AN:

50978

Middle Eastern (MID)

AF:

0.00401

AC:

AN:

5238

European-Non Finnish (NFE)

AF:

0.000891

AC:

891

AN:

999508

Other (OTH)

AF:

0.00181

AC:

100

AN:

55322

⚠️ 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: 0.239

Heterozygous variant carriers

435

870

1306

1741

2176

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000190

AC:

AN:

105260

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

AN XY:

51142

show subpopulations

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

African (AFR)

AF:

0.000273

AC:

AN:

25664

American (AMR)

AF:

0.000354

AC:

AN:

11298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2428

East Asian (EAS)

AF:

0.000319

AC:

AN:

3138

South Asian (SAS)

AF:

0.000348

AC:

AN:

2876

European-Finnish (FIN)

AF:

0.000141

AC:

AN:

7112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.0000992

AC:

AN:

50406

Other (OTH)

AF:

0.000669

AC:

AN:

1494

⚠️ 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: 0.237

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:

0.0301

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.086

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over