rs148581741

Variant names:

• chr11-1018419-G-A
• rs148581741
• NM_005961.3:c.4382C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1018419-G-A
• chr11-1018419-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005961.3(MUC6):​c.4382C>T​(p.Thr1461Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 151,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 55)
  • Exomes 𝑓: 0.00024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -6.16
• Publications: 4 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=0.001678884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC6	NM_005961.3	c.4382C>T	p.Thr1461Ile	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.4382C>T	p.Thr1461Ile	missense_variant	Exon 31 of 33	5	NM_005961.3	ENSP00000406861.2

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 19 AN: 151012 Hom.: 0 Cov.: 55

Gnomad AFR AF: 0.000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000587

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000482

GnomAD2 exomes AF: 0.102 AC: 8806 AN: 86506 AF XY: 0.112

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.0741

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0735

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000236 AC: 282 AN: 1194398 Hom.: 0 Cov.: 211 AF XY: 0.000214 AC XY: 128 AN XY: 599146

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

African (AFR) AF: 0.00113 AC: 30 AN: 26632

American (AMR) AF: 0.0000490 AC: 2 AN: 40808

Ashkenazi Jewish (ASJ) AF: 0.000172 AC: 4 AN: 23228

East Asian (EAS) AF: 0.000108 AC: 4 AN: 37062

South Asian (SAS) AF: 0.000117 AC: 9 AN: 76736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51622

Middle Eastern (MID) AF: 0.000196 AC: 1 AN: 5092

European-Non Finnish (NFE) AF: 0.000244 AC: 215 AN: 881970

Other (OTH) AF: 0.000332 AC: 17 AN: 51248

⚠️ 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 AF: 0.000126 AC: 19 AN: 151126 Hom.: 0 Cov.: 55 AF XY: 0.000149 AC XY: 11 AN XY: 73844

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

African (AFR) AF: 0.000268 AC: 11 AN: 41106

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.000588 AC: 3 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67696

Other (OTH) AF: 0.000477 AC: 1 AN: 2096

⚠️ 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: 0.0988 Hom.: 0

ExAC AF: 0.318 AC: 38586

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.074
DANN	Benign	0.74
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-6.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N
Sift	Benign	0.26	T
Sift4G	Benign	0.088	T
Vest4		0.020
ClinPred		0.0065	T
GERP RS		-4.7
Varity_R		0.023
gMVP		0.20
Mutation Taster		=99/1	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: rs148581741; hg19: chr11-1018419; COSMIC: COSV70133118; COSMIC: COSV70133118;