Genetic Variant MUC6:p.Thr1889Thr (chr11-1017134-G-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005961.3(MUC6):c.5667C>A(p.Thr1889Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 129)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC6
NM_005961.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.20

Publications

1 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 11-1017134-G-T is Benign according to our data. Variant chr11-1017134-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641103.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

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.5667C>A	p.Thr1889Thr	synonymous	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.5667C>A	p.Thr1889Thr	synonymous	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes

AF:

0.000332

AC:

AN:

105540

Hom.:

Cov.:

129

show subpopulations

Gnomad AFR

AF:

0.000167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000882

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000264

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000679

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000329

Gnomad OTH

AF:

0.000710

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1458738

Hom.:

Cov.:

320

AF XY:

0.00

AC XY:

AN XY:

725650

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109980

Other (OTH)

AF:

0.00

AC:

AN:

60192

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000331

AC:

AN:

105600

Hom.:

Cov.:

129

AF XY:

0.000331

AC XY:

AN XY:

51360

show subpopulations

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

African (AFR)

AF:

0.000167

AC:

AN:

30006

American (AMR)

AF:

0.000881

AC:

AN:

9076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2610

East Asian (EAS)

AF:

0.000264

AC:

AN:

3792

South Asian (SAS)

AF:

0.00

AC:

AN:

3358

European-Finnish (FIN)

AF:

0.000679

AC:

AN:

5890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.000329

AC:

AN:

48626

Other (OTH)

AF:

0.000703

AC:

AN:

1422

⚠️ 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: 0.272

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:

0.0238

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.55

(source)

DANN

Benign

0.53

PhyloP100

-3.2

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over