NM_005961.3:c.4527C>G

Variant names:

• chr11-1018274-G-C
• rs79073076
• NM_005961.3:c.4527C>G

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.4527C>G​(p.Thr1509Thr) 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 0.0073 (0 hom., cov: 50)
  • Exomes 𝑓: 0.000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.544
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-1018274-G-C is Benign according to our data. Variant chr11-1018274-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2641107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.544 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.4527C>G	p.Thr1509Thr	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.4527C>G	p.Thr1509Thr	synonymous	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 695 AN: 95754 Hom.: 0 Cov.: 50

Gnomad AFR AF: 0.00607

Gnomad AMI AF: 0.00368

Gnomad AMR AF: 0.00964

Gnomad ASJ AF: 0.00464

Gnomad EAS AF: 0.00252

Gnomad SAS AF: 0.00659

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0156

Gnomad NFE AF: 0.00727

Gnomad OTH AF: 0.00664

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000249 AC: 34 AN: 1368074 Hom.: 0 Cov.: 153 AF XY: 0.0000295 AC XY: 20 AN XY: 678104

⚠️ 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: 31370

American (AMR) AF: 0.000164 AC: 6 AN: 36642

Ashkenazi Jewish (ASJ) AF: 0.0000854 AC: 2 AN: 23416

East Asian (EAS) AF: 0.00 AC: 0 AN: 37956

South Asian (SAS) AF: 0.00 AC: 0 AN: 72840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.0000237 AC: 25 AN: 1054140

Other (OTH) AF: 0.0000178 AC: 1 AN: 56230

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00726 AC: 696 AN: 95830 Hom.: 0 Cov.: 50 AF XY: 0.00836 AC XY: 391 AN XY: 46778

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

African (AFR) AF: 0.00605 AC: 168 AN: 27768

American (AMR) AF: 0.00963 AC: 93 AN: 9660

Ashkenazi Jewish (ASJ) AF: 0.00464 AC: 10 AN: 2156

East Asian (EAS) AF: 0.00252 AC: 9 AN: 3568

South Asian (SAS) AF: 0.00692 AC: 22 AN: 3180

European-Finnish (FIN) AF: 0.0127 AC: 82 AN: 6444

Middle Eastern (MID) AF: 0.0170 AC: 3 AN: 176

European-Non Finnish (NFE) AF: 0.00727 AC: 298 AN: 40964

Other (OTH) AF: 0.00657 AC: 9 AN: 1370

⚠️ 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: 0.0287 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	3.4
DANN	Benign	0.36
PhyloP100		-0.54
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: rs79073076; hg19: chr11-1018274;