Genetic Variant MUC19:c.20617+56G>T (chr12-40521024-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173600.2(MUC19):c.20563+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 978,358 control chromosomes in the GnomAD database, including 17,866 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 0.19 ( 2693 hom., cov: 33)

Exomes 𝑓: 0.19 ( 15173 hom. )

Consequence

MUC19
NM_173600.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.737

Publications

6 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:

ENSG00000296211 (HGNC:):

ENSG00000296211 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173600.2. 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
	MUC19	NM_173600.2		c.20563+56G>T		intron	N/A	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MUC19	ENST00000454784.10	TSL:5	c.20617+56G>T	intron	N/A	ENSP00000508949.1
MUC19	ENST00000398702.7	TSL:4	n.253+56G>T	intron	N/A
ENSG00000296211	ENST00000737355.1		n.441-2007C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28251

AN:

151986

Hom.:

2692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.191

AC:

157418

AN:

826254

Hom.:

15173

AF XY:

0.190

AC XY:

72877

AN XY:

382926

show subpopulations

African (AFR)

AF:

0.178

AC:

2747

AN:

15456

American (AMR)

AF:

0.200

AC:

224

AN:

1118

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

826

AN:

5200

East Asian (EAS)

AF:

0.210

AC:

786

AN:

3746

South Asian (SAS)

AF:

0.138

AC:

2328

AN:

16812

European-Finnish (FIN)

AF:

0.181

AC:

1673

AN:

9224

Middle Eastern (MID)

AF:

0.147

AC:

477

AN:

3240

European-Non Finnish (NFE)

AF:

0.193

AC:

143618

AN:

744208

Other (OTH)

AF:

0.174

AC:

4739

AN:

27250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5878

11756

17635

23513

29391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6856

13712

20568

27424

34280

<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:

0.186

AC:

28263

AN:

152104

Hom.:

2693

Cov.:

AF XY:

0.183

AC XY:

13631

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.171

AC:

7083

AN:

41496

American (AMR)

AF:

0.188

AC:

2865

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

547

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1055

AN:

5168

South Asian (SAS)

AF:

0.129

AC:

623

AN:

4826

European-Finnish (FIN)

AF:

0.182

AC:

1928

AN:

10578

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13445

AN:

67980

Other (OTH)

AF:

0.179

AC:

377

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1190

2380

3570

4760

5950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.186

Hom.:

363

Bravo

AF:

0.188

Asia WGS

AF:

0.150

AC:

525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.99

(source)

DANN

Benign

0.35

PhyloP100

-0.74

Mutation Taster

=100/0

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