11-1018116-T-G

Variant names:

• chr11-1018116-T-G
• rs10902269
• NM_005961.3:c.4685A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 15/21 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
• Publications: 16 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: Likely_benign. The variant received -4 ACMG points.

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

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.4685A>C	p.Asn1562Thr	missense	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.4685A>C	p.Asn1562Thr	missense	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.432 AC: 46804 AN: 108432 Hom.: 0 Cov.: 42

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

GnomAD2 exomes AF: 0.489 AC: 84235 AN: 172418 AF XY: 0.490

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.490

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.493

Gnomad FIN exome AF: 0.458

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.490

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

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

African (AFR) AF: 0.481 AC: 13508 AN: 28068

American (AMR) AF: 0.490 AC: 18786 AN: 38304

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 10776 AN: 22126

East Asian (EAS) AF: 0.490 AC: 16997 AN: 34696

South Asian (SAS) AF: 0.488 AC: 35402 AN: 72566

European-Finnish (FIN) AF: 0.485 AC: 20432 AN: 42158

Middle Eastern (MID) AF: 0.472 AC: 2143 AN: 4538

European-Non Finnish (NFE) AF: 0.475 AC: 400234 AN: 842986

Other (OTH) AF: 0.480 AC: 22904 AN: 47704

⚠️ 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: InbreedingCoeff AF: 0.432 AC: 46868 AN: 108558 Hom.: 0 Cov.: 42 AF XY: 0.430 AC XY: 22735 AN XY: 52874

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

African (AFR) AF: 0.433 AC: 12871 AN: 29692

American (AMR) AF: 0.419 AC: 4481 AN: 10692

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1105 AN: 2510

East Asian (EAS) AF: 0.444 AC: 1695 AN: 3820

South Asian (SAS) AF: 0.433 AC: 1398 AN: 3228

European-Finnish (FIN) AF: 0.419 AC: 3103 AN: 7404

Middle Eastern (MID) AF: 0.454 AC: 109 AN: 240

European-Non Finnish (NFE) AF: 0.433 AC: 21108 AN: 48706

Other (OTH) AF: 0.440 AC: 687 AN: 1562

⚠️ 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: 0.457 Hom.: 0

ExAC AF: 0.322 AC: 38987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.4
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
Mutation Taster		=82/18	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: rs10902269; hg19: chr11-1018116; COSMIC: COSV70132362; COSMIC: COSV70132362;