rs1856718594

Variant names:

• chr11-1018264-G-GA
• rs1856718594
• NM_005961.3:c.4536_4537insT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4536_4537insT	p.His1513SerfsTer24	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.4536_4537insT	p.His1513SerfsTer24	frameshift	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.0000295 AC: 4 AN: 135598 Hom.: 0 Cov.: 56

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: 5 AN: 1400258 Hom.: 0 Cov.: 150 AF XY: 0.00000574 AC XY: 4 AN XY: 697090

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

African (AFR) AF: 0.00 AC: 0 AN: 32194

American (AMR) AF: 0.00 AC: 0 AN: 42008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39364

South Asian (SAS) AF: 0.0000487 AC: 4 AN: 82218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1063068

Other (OTH) AF: 0.00 AC: 0 AN: 58256

⚠️ 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.

GnomAD4 genome AF: 0.0000295 AC: 4 AN: 135698 Hom.: 0 Cov.: 56 AF XY: 0.0000605 AC XY: 4 AN XY: 66100

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

African (AFR) AF: 0.0000269 AC: 1 AN: 37162

American (AMR) AF: 0.0000739 AC: 1 AN: 13528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3138

East Asian (EAS) AF: 0.000220 AC: 1 AN: 4554

South Asian (SAS) AF: 0.00 AC: 0 AN: 4258

European-Finnish (FIN) AF: 0.000108 AC: 1 AN: 9286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60838

Other (OTH) AF: 0.00 AC: 0 AN: 1872

⚠️ 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.

Alfa AF: 0.00180 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8
Mutation Taster		=90/110	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1856718594; hg19: chr11-1018264;