chr11-1017495-ATGC-A

Variant names:

• chr11-1017495-ATGC-A
• rs752315234
• NM_005961.3:c.5303_5305delGCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_005961.3(MUC6):​c.5303_5305delGCA​(p.Ser1768del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 2 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 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005961.3. Strenght limited to Supporting due to length of the change: 1aa.

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.5303_5305delGCA	p.Ser1768del	disruptive_inframe_deletion	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.5303_5305delGCA	p.Ser1768del	disruptive_inframe_deletion	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.00733 AC: 464 AN: 63282 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00319

Gnomad ASJ AF: 0.00282

Gnomad EAS AF: 0.00261

Gnomad SAS AF: 0.00390

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.00915

GnomAD2 exomes AF: 0.00421 AC: 449 AN: 106540 AF XY: 0.00525

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00321

Gnomad NFE exome AF: 0.00406

Gnomad OTH exome AF: 0.00101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00162 AC: 1846 AN: 1137744 Hom.: 0 AF XY: 0.00208 AC XY: 1148 AN XY: 550806

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

African (AFR) AF: 0.00436 AC: 102 AN: 23400

American (AMR) AF: 0.00988 AC: 195 AN: 19740

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 159 AN: 15512

East Asian (EAS) AF: 0.0000391 AC: 1 AN: 25594

South Asian (SAS) AF: 0.0103 AC: 479 AN: 46328

European-Finnish (FIN) AF: 0.00374 AC: 124 AN: 33124

Middle Eastern (MID) AF: 0.00174 AC: 7 AN: 4018

European-Non Finnish (NFE) AF: 0.000770 AC: 713 AN: 925452

Other (OTH) AF: 0.00148 AC: 66 AN: 44576

⚠️ 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;InbreedingCoeff AF: 0.00734 AC: 465 AN: 63344 Hom.: 0 Cov.: 0 AF XY: 0.00701 AC XY: 224 AN XY: 31970

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

African (AFR) AF: 0.0274 AC: 374 AN: 13634

American (AMR) AF: 0.00318 AC: 23 AN: 7230

Ashkenazi Jewish (ASJ) AF: 0.00282 AC: 4 AN: 1418

East Asian (EAS) AF: 0.00262 AC: 5 AN: 1912

South Asian (SAS) AF: 0.00389 AC: 8 AN: 2054

European-Finnish (FIN) AF: 0.000566 AC: 3 AN: 5298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.00132 AC: 40 AN: 30282

Other (OTH) AF: 0.00913 AC: 8 AN: 876

⚠️ 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: 0.0715 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.23
Mutation Taster		=88/12	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: rs752315234; hg19: chr11-1017495; COSMIC: COSV70133033; COSMIC: COSV70133033;