Genetic Variant ENST00000454784.10:c.2372G>T (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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
MUC19	NM_173600.2 link	c.2372G>T	p.Arg791Leu	missense_variant	Exon 20 of 172	NP_775871.2	Q7Z5P9-1
LOC105369736	XR_007063562.1 link	n.75-7758C>A		intron_variant	Intron 1 of 4
LOC105369736	XR_944866.1 link	n.75-7758C>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10 link	c.2372G>T	p.Arg791Leu	missense_variant	Exon 20 of 173	5		ENSP00000508949.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over