Genetic Variant ENST00000454784.10:c.2407G>C (chr12-40429552-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000454784.10(MUC19):c.2407G>C(p.Asp803His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,283,110 control chromosomes in the GnomAD database, including 10,100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.095 ( 1011 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9089 hom. )

Consequence

MUC19
ENST00000454784.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

Publications

13 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.1).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	NM_173600.2		c.2407G>C	p.Asp803His	missense	Exon 21 of 172	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MUC19	ENST00000454784.10	TSL:5	c.2407G>C	p.Asp803His	missense	Exon 21 of 173	ENSP00000508949.1
ENSG00000258167	ENST00000552757.2	TSL:5	n.66-9241C>G		intron	N/A
ENSG00000258167	ENST00000724141.1		n.78-9241C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0951

AC:

14460

AN:

152096

Hom.:

1011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0865

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0845

GnomAD2 exomes

AF:

0.103

AC:

13604

AN:

132220

AF XY:

0.0993

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0679

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.120

AC:

135563

AN:

1130896

Hom.:

9089

Cov.:

AF XY:

0.117

AC XY:

65036

AN XY:

554198

show subpopulations

African (AFR)

AF:

0.0204

AC:

472

AN:

23182

American (AMR)

AF:

0.0673

AC:

1636

AN:

24318

Ashkenazi Jewish (ASJ)

AF:

0.0886

AC:

1350

AN:

15232

East Asian (EAS)

AF:

0.0181

AC:

208

AN:

11504

South Asian (SAS)

AF:

0.0370

AC:

2689

AN:

72604

European-Finnish (FIN)

AF:

0.238

AC:

6478

AN:

27208

Middle Eastern (MID)

AF:

0.0812

AC:

349

AN:

4296

European-Non Finnish (NFE)

AF:

0.129

AC:

117915

AN:

911694

Other (OTH)

AF:

0.109

AC:

4466

AN:

40858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

4929

9859

14788

19718

24647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4860

9720

14580

19440

24300

<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:

0.0950

AC:

14458

AN:

152214

Hom.:

1011

Cov.:

AF XY:

0.0977

AC XY:

7269

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0260

AC:

1079

AN:

41542

American (AMR)

AF:

0.0735

AC:

1125

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0865

AC:

300

AN:

3470

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5176

South Asian (SAS)

AF:

0.0306

AC:

148

AN:

4832

European-Finnish (FIN)

AF:

0.247

AC:

2614

AN:

10570

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8681

AN:

68016

Other (OTH)

AF:

0.0836

AC:

176

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

651

1301

1952

2602

3253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.111

Hom.:

355

Bravo

AF:

0.0814

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

2.5

Mutation Taster

=97/3

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