11-1017466-T-C

Variant names:

• chr11-1017466-T-C
• rs201054567
• NM_005961.3:c.5335A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005961.3(MUC6):​c.5335A>G​(p.Arg1779Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 982,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (0 hom., cov: 119)
  • Exomes 𝑓: 0.031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015816987).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3	c.5335A>G	p.Arg1779Gly	missense_variant	Exon 31 of 33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7	c.5335A>G	p.Arg1779Gly	missense_variant	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15606 AN: 78530 Hom.: 0 Cov.: 119 FAILED QC

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.0306 AC: 30071 AN: 982060 Hom.: 0 Cov.: 306 AF XY: 0.0351 AC XY: 16517 AN XY: 471208

Gnomad4 AFR exome AF: 0.0512

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.0612

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.0870

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.199 AC: 15627 AN: 78576 Hom.: 0 Cov.: 119 AF XY: 0.197 AC XY: 7685 AN XY: 39090

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.215

ExAC AF: 0.188 AC: 22066

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.013
DANN	Benign	0.40
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0050	N
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.29	N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.0050
Sift	Benign	0.98	T
Sift4G	Benign	0.43	T
Polyphen		0.025	B
Vest4		0.0060
MPC		0.12
ClinPred		0.092	T
GERP RS		0.018
Varity_R		0.046
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs201054567; hg19: chr11-1017466; COSMIC: COSV70144374; COSMIC: COSV70144374;