rs10902269

chr11-1018116-T-Achr11-1018116-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005961.3(MUC6):c.4685A>T(p.Asn1562Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 42)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040213972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC6	NM_005961.3	c.4685A>T	p.Asn1562Ile	missense_variant	31/33	ENST00000421673.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC6	ENST00000421673.7	c.4685A>T	p.Asn1562Ile	missense_variant	31/33	5	NM_005961.3	P1

Frequencies

GnomAD3 genomes Cov.: 42

GnomAD4 exome Cov.: 107

GnomAD4 genome Cov.: 42

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Benign	0.51
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.052
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.054	T
Polyphen		0.012	B
Vest4		0.11
MutPred		0.36		Gain of sheet (P = 0.0028);
MVP		0.16
MPC		0.11
ClinPred		0.089	T
GERP RS		-0.083
Varity_R		0.11
gMVP		0.30

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;