Genetic Variant MUC19:p.Arg791Leu (chr12-40428069-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000454784.10(MUC19):c.2372G>T(p.Arg791Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0294 in 1,303,216 control chromosomes in the GnomAD database, including 1,754 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 229 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1525 hom. )

Consequence

MUC19
ENST00000454784.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.06

Publications

10 publications found

Variant links:

Genes affected

MUC19 (HGNC:14362): (mucin 19, oligomeric) This gene encodes a member of the gel-forming mucin protein family. Mucin family members are glycoproteins that have tandem repeats which are extensively O-glycosylated. The structural features of mucin proteins are responsible for the gel-like properties of mucus. The encoded protein may be involved in disruption of the ocular surface in Sjogren syndrome. [provided by RefSeq, Apr 2014]

MUC19 links:

ENSG00000258167 (HGNC:):

ENSG00000258167 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454784.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	NM_173600.2		c.2372G>T	p.Arg791Leu	missense	Exon 20 of 172	NP_775871.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MUC19	ENST00000454784.10	TSL:5	c.2372G>T	p.Arg791Leu	missense	Exon 20 of 173	ENSP00000508949.1
MUC19	ENST00000543564.2	TSL:5	n.681G>T		splice_region non_coding_transcript_exon	Exon 3 of 3
ENSG00000258167	ENST00000552757.2	TSL:5	n.66-7758C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4933

AN:

152062

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00780

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.0404

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0422

GnomAD2 exomes

AF:

0.0709

AC:

10620

AN:

149822

AF XY:

0.0667

show subpopulations

Gnomad AFR exome

AF:

0.00552

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.0370

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0652

GnomAD4 exome

AF:

0.0290

AC:

33415

AN:

1151036

Hom.:

1525

Cov.:

AF XY:

0.0309

AC XY:

17468

AN XY:

564402

show subpopulations

African (AFR)

AF:

0.00565

AC:

138

AN:

24406

American (AMR)

AF:

0.219

AC:

6186

AN:

28202

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

931

AN:

15904

East Asian (EAS)

AF:

0.0378

AC:

485

AN:

12834

South Asian (SAS)

AF:

0.0956

AC:

7267

AN:

76000

European-Finnish (FIN)

AF:

0.0283

AC:

776

AN:

27400

Middle Eastern (MID)

AF:

0.0937

AC:

412

AN:

4396

European-Non Finnish (NFE)

AF:

0.0171

AC:

15732

AN:

920266

Other (OTH)

AF:

0.0357

AC:

1488

AN:

41628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

1368

2736

4104

5472

6840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

794

1588

2382

3176

3970

<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

AF:

0.0325

AC:

4940

AN:

152180

Hom.:

229

Cov.:

AF XY:

0.0360

AC XY:

2677

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00778

AC:

323

AN:

41526

American (AMR)

AF:

0.117

AC:

1793

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3468

East Asian (EAS)

AF:

0.0403

AC:

209

AN:

5180

South Asian (SAS)

AF:

0.104

AC:

498

AN:

4804

European-Finnish (FIN)

AF:

0.0288

AC:

306

AN:

10610

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0215

AC:

1460

AN:

68006

Other (OTH)

AF:

0.0417

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

220

440

659

879

1099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0312

Hom.:

313

Bravo

AF:

0.0389

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

4.1

Mutation Taster

=93/7

polymorphism (auto)

(source)

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