Genetic Variant MUC5AC:p.Pro4595Pro (chr11-1191930-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001304359.2(MUC5AC):c.13785C>T(p.Pro4595Pro) 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC5AC
NM_001304359.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.92

Publications

3 publications found

Variant links:

Genes affected

MUC5AC (HGNC:7515): (mucin 5AC, oligomeric mucus/gel-forming) Predicted to be an extracellular matrix structural constituent. Involved in phosphatidylinositol-mediated signaling. Located in cytoplasm; extracellular space; and mucus layer. Implicated in dry eye syndrome. Biomarker of several diseases, including Sjogren's syndrome; biliary tract disease (multiple); cystic fibrosis; eye disease (multiple); and pancreatic cancer (multiple). [provided by Alliance of Genome Resources, Apr 2022]

MUC5AC links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-1191930-C-T is Benign according to our data. Variant chr11-1191930-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641170.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.92 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304359.2. 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
	MUC5AC	NM_001304359.2	MANE Select	c.13785C>T	p.Pro4595Pro	synonymous	Exon 31 of 49	NP_001291288.1	P98088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC5AC	ENST00000621226.2	TSL:5 MANE Select	c.13785C>T	p.Pro4595Pro	synonymous	Exon 31 of 49	ENSP00000485659.1	P98088

Frequencies

GnomAD3 genomes

AF:

0.000120

AC:

AN:

141870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000209

Gnomad SAS

AF:

0.000229

Gnomad FIN

AF:

0.000207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000311

Gnomad OTH

AF:

0.000520

GnomAD2 exomes

AF:

0.00961

AC:

497

AN:

51702

AF XY:

0.00759

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00754

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.00557

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.0000198

AC:

AN:

607276

Hom.:

Cov.:

AF XY:

0.0000241

AC XY:

AN XY:

331816

show subpopulations

African (AFR)

AF:

0.0000575

AC:

AN:

17388

American (AMR)

AF:

0.00

AC:

AN:

43472

Ashkenazi Jewish (ASJ)

AF:

0.0000480

AC:

AN:

20850

East Asian (EAS)

AF:

0.00

AC:

AN:

35860

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69564

European-Finnish (FIN)

AF:

0.0000534

AC:

AN:

37440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.0000173

AC:

AN:

346024

Other (OTH)

AF:

0.0000307

AC:

AN:

32558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000120

AC:

AN:

141978

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

AN XY:

69416

show subpopulations

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

African (AFR)

AF:

0.000263

AC:

AN:

38036

American (AMR)

AF:

0.00

AC:

AN:

14432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3322

East Asian (EAS)

AF:

0.000210

AC:

AN:

4770

South Asian (SAS)

AF:

0.000229

AC:

AN:

4362

European-Finnish (FIN)

AF:

0.000207

AC:

AN:

9670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.0000311

AC:

AN:

64360

Other (OTH)

AF:

0.000514

AC:

AN:

1944

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000244349), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0368

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.75

PhyloP100

-4.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over