11-1016825-G-A

Variant names:

• chr11-1016825-G-A
• rs775937889
• NM_005961.3:c.5976C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005961.3(MUC6):​c.5976C>T​(p.Thr1992Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 113,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 259)
  • Exomes 𝑓: 0.000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54
• Publications: 4 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-1016825-G-A is Benign according to our data. Variant chr11-1016825-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 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.5976C>T	p.Thr1992Thr	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.5976C>T	p.Thr1992Thr	synonymous	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.000875 AC: 99 AN: 113088 Hom.: 0 Cov.: 259

Gnomad AFR AF: 0.00185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000765

Gnomad SAS AF: 0.000575

Gnomad FIN AF: 0.000831

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00128

GnomAD2 exomes AF: 0.000535 AC: 92 AN: 171828 AF XY: 0.000359

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.000363

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00185

Gnomad FIN exome AF: 0.000373

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000226 AC: 30 AN: 1326436 Hom.: 0 Cov.: 541 AF XY: 0.0000275 AC XY: 18 AN XY: 655396

⚠️ 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: 29772

American (AMR) AF: 0.000138 AC: 4 AN: 28938

Ashkenazi Jewish (ASJ) AF: 0.0000438 AC: 1 AN: 22806

East Asian (EAS) AF: 0.00 AC: 0 AN: 33552

South Asian (SAS) AF: 0.0000148 AC: 1 AN: 67690

European-Finnish (FIN) AF: 0.0000463 AC: 2 AN: 43156

Middle Eastern (MID) AF: 0.000197 AC: 1 AN: 5078

European-Non Finnish (NFE) AF: 0.0000163 AC: 17 AN: 1041452

Other (OTH) AF: 0.0000741 AC: 4 AN: 53992

⚠️ 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: 0.000875 AC: 99 AN: 113140 Hom.: 0 Cov.: 259 AF XY: 0.000841 AC XY: 46 AN XY: 54728

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

African (AFR) AF: 0.00185 AC: 55 AN: 29758

American (AMR) AF: 0.00119 AC: 12 AN: 10126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2706

East Asian (EAS) AF: 0.000768 AC: 3 AN: 3904

South Asian (SAS) AF: 0.000575 AC: 2 AN: 3476

European-Finnish (FIN) AF: 0.000831 AC: 6 AN: 7224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.000356 AC: 19 AN: 53396

Other (OTH) AF: 0.00127 AC: 2 AN: 1576

⚠️ 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: 0.0262 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.46
DANN	Benign	0.50
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs775937889; hg19: chr11-1016825; COSMIC: COSV70142672; COSMIC: COSV70142672;