11-1018116-T-G

Position:

• chr11-1018116-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005961.3(MUC6):​c.4685A>C​(p.Asn1562Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.43 (0 hom., cov: 42)
  • Exomes 𝑓: 0.48 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013881326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC6	NM_005961.3	c.4685A>C	p.Asn1562Thr	missense_variant	31/33	ENST00000421673.7	NP_005952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC6	ENST00000421673.7	c.4685A>C	p.Asn1562Thr	missense_variant	31/33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 46804 AN: 108432 Hom.: 0 Cov.: 42 FAILED QC

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.440

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.478 AC: 541182 AN: 1133146 Hom.: 0 Cov.: 107 AF XY: 0.479 AC XY: 273000 AN XY: 569802

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.432 AC: 46868 AN: 108558 Hom.: 0 Cov.: 42 AF XY: 0.430 AC XY: 22735 AN XY: 52874

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.440

Alfa AF: 0.457 Hom.: 0

ExAC AF: 0.322 AC: 38987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.67
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0034	N
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.0	N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.090
ClinPred		0.0064	T
GERP RS		-0.083
Varity_R		0.033
gMVP		0.14

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: rs10902269; hg19: chr11-1018116; COSMIC: COSV70132362; COSMIC: COSV70132362;