NM_005961.3:c.5911C>T

Variant names:

• chr11-1016890-G-A
• rs113508205
• NM_005961.3:c.5911C>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.5911C>T​(p.Pro1971Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.48 (1 hom., cov: 187)
  • Exomes 𝑓: 0.47 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -5.41
• Publications: 12 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=0.0014880002).

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.5911C>T	p.Pro1971Ser	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.5911C>T	p.Pro1971Ser	missense	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.478 AC: 50632 AN: 105982 Hom.: 1 Cov.: 187

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.470

GnomAD2 exomes AF: 0.483 AC: 76858 AN: 159164 AF XY: 0.485

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.487

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.466

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.472 AC: 463690 AN: 981546 Hom.: 0 Cov.: 461 AF XY: 0.474 AC XY: 235911 AN XY: 497896

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

African (AFR) AF: 0.491 AC: 13943 AN: 28408

American (AMR) AF: 0.485 AC: 15488 AN: 31904

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 9635 AN: 19954

East Asian (EAS) AF: 0.489 AC: 17324 AN: 35436

South Asian (SAS) AF: 0.481 AC: 35470 AN: 73676

European-Finnish (FIN) AF: 0.470 AC: 18507 AN: 39378

Middle Eastern (MID) AF: 0.474 AC: 1927 AN: 4064

European-Non Finnish (NFE) AF: 0.469 AC: 331361 AN: 706622

Other (OTH) AF: 0.476 AC: 20035 AN: 42104

⚠️ 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: 0.478 AC: 50666 AN: 106054 Hom.: 1 Cov.: 187 AF XY: 0.477 AC XY: 24979 AN XY: 52348

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

African (AFR) AF: 0.485 AC: 16045 AN: 33076

American (AMR) AF: 0.468 AC: 4630 AN: 9900

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1138 AN: 2364

East Asian (EAS) AF: 0.484 AC: 1990 AN: 4112

South Asian (SAS) AF: 0.482 AC: 1777 AN: 3686

European-Finnish (FIN) AF: 0.476 AC: 3468 AN: 7292

Middle Eastern (MID) AF: 0.476 AC: 99 AN: 208

European-Non Finnish (NFE) AF: 0.474 AC: 20551 AN: 43366

Other (OTH) AF: 0.469 AC: 690 AN: 1470

⚠️ 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: 0.445 Hom.: 0

ExAC AF: 0.199 AC: 24136

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		-5.4
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.0030	B
Vest4		0.024
MPC		0.43
ClinPred		0.011	T
GERP RS		-6.2
Varity_R		0.023
gMVP		0.10
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: rs113508205; hg19: chr11-1016890; COSMIC: COSV70132142; COSMIC: COSV70132142;