chr11-1017134-G-C

Variant names:

• chr11-1017134-G-C
• rs201950836
• NM_005961.3:c.5667C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005961.3(MUC6):​c.5667C>G​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1889T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 129)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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>G	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>G	p.Thr1889Thr	synonymous	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 324 AN: 92610 Hom.: 0 Cov.: 129

Gnomad AFR AF: 0.00209

Gnomad AMI AF: 0.00341

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.000900

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.00354

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00685

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.00239

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458256 Hom.: 0 Cov.: 320 AF XY: 0.00 AC XY: 0 AN XY: 725456

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109622

Other (OTH) AF: 0.00 AC: 0 AN: 60156

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00350 AC: 324 AN: 92656 Hom.: 0 Cov.: 129 AF XY: 0.00398 AC XY: 180 AN XY: 45188

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

African (AFR) AF: 0.00212 AC: 57 AN: 26922

American (AMR) AF: 0.00575 AC: 45 AN: 7822

Ashkenazi Jewish (ASJ) AF: 0.000900 AC: 2 AN: 2222

East Asian (EAS) AF: 0.00169 AC: 6 AN: 3550

South Asian (SAS) AF: 0.00355 AC: 11 AN: 3098

European-Finnish (FIN) AF: 0.0105 AC: 54 AN: 5140

Middle Eastern (MID) AF: 0.00746 AC: 1 AN: 134

European-Non Finnish (NFE) AF: 0.00344 AC: 144 AN: 41920

Other (OTH) AF: 0.00158 AC: 2 AN: 1262

⚠️ 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: 0.0227 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.47
PhyloP100		-3.2

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: rs201950836; hg19: chr11-1017134;