NM_005961.3:c.4401C>T

Variant names:

• chr11-1018400-G-A
• rs748438008
• NM_005961.3:c.4401C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005961.3(MUC6):​c.4401C>T​(p.His1467His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 57)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC6 NM_005961.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.02
• Publications: 2 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-1018400-G-A is Benign according to our data. Variant chr11-1018400-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.02 with no splicing effect.

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.4401C>T	p.His1467His	synonymous	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.4401C>T	p.His1467His	synonymous	Exon 31 of 33	ENSP00000406861.2	Q6W4X9

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 29 AN: 130660 Hom.: 0 Cov.: 57

Gnomad AFR AF: 0.000351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000230

Gnomad ASJ AF: 0.000324

Gnomad EAS AF: 0.000223

Gnomad SAS AF: 0.000724

Gnomad FIN AF: 0.000323

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000101

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000518 AC: 12 AN: 231860 AF XY: 0.0000238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000623

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000150 AC: 21 AN: 1401352 Hom.: 0 Cov.: 207 AF XY: 0.0000100 AC XY: 7 AN XY: 697866

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

African (AFR) AF: 0.0000313 AC: 1 AN: 31946

American (AMR) AF: 0.0000235 AC: 1 AN: 42506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.000154 AC: 6 AN: 39052

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52252

Middle Eastern (MID) AF: 0.000187 AC: 1 AN: 5358

European-Non Finnish (NFE) AF: 0.00000753 AC: 8 AN: 1062770

Other (OTH) AF: 0.0000343 AC: 2 AN: 58274

⚠️ 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: AS_VQSR AF: 0.000222 AC: 29 AN: 130734 Hom.: 0 Cov.: 57 AF XY: 0.000252 AC XY: 16 AN XY: 63454

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

African (AFR) AF: 0.000350 AC: 12 AN: 34240

American (AMR) AF: 0.000230 AC: 3 AN: 13060

Ashkenazi Jewish (ASJ) AF: 0.000324 AC: 1 AN: 3086

East Asian (EAS) AF: 0.000224 AC: 1 AN: 4460

South Asian (SAS) AF: 0.000724 AC: 3 AN: 4144

European-Finnish (FIN) AF: 0.000323 AC: 3 AN: 9276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000101 AC: 6 AN: 59590

Other (OTH) AF: 0.00 AC: 0 AN: 1816

⚠️ 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: 0.00386 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748438008; hg19: chr11-1018400;