Variant 11-1018264-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005961.3(MUC6):c.4536_4537insT(p.His1513SerfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,535,956 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 56)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

MUC6
NM_005961.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -1.81

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 made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC6	NM_005961.3 linkuse as main transcript	c.4536_4537insT	p.His1513SerfsTer24	frameshift_variant	31/33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7 linkuse as main transcript	c.4536_4537insT	p.His1513SerfsTer24	frameshift_variant	31/33	5	NM_005961.3	ENSP00000406861	P1

Frequencies

GnomAD3 genomes

AF:

0.0000295

AC:

AN:

135598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000219

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1400258

Hom.:

Cov.:

150

AF XY:

0.00000574

AC XY:

AN XY:

697090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.41e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000295

AC:

AN:

135698

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

66100

show subpopulations

Gnomad4 AFR

AF:

0.0000269

Gnomad4 AMR

AF:

0.0000739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000220

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000108

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00180

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Lung cancer

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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