Genetic Variant MUC19:p.Asp1235Asp (chr12-40441144-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_173600.2(MUC19):c.3705C>T(p.Asp1235Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,303,966 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

MUC19
NM_173600.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.691

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 12-40441144-C-T is Benign according to our data. Variant chr12-40441144-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642861.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.691 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

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.3705C>T	p.Asp1235Asp	synonymous	Exon 31 of 172	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MUC19	ENST00000454784.10	TSL:5	c.3705C>T	p.Asp1235Asp	synonymous	Exon 31 of 173	ENSP00000508949.1
ENSG00000258167	ENST00000552757.2	TSL:5	n.65+2679G>A		intron	N/A
ENSG00000258167	ENST00000724141.1		n.77+2679G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

482

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00466

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00322

AC:

483

AN:

149898

AF XY:

0.00321

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00393

Gnomad EAS exome

AF:

0.0000927

Gnomad FIN exome

AF:

0.000890

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00408

AC:

4701

AN:

1151680

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

2299

AN XY:

564676

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

24412

American (AMR)

AF:

0.00223

AC:

AN:

28254

Ashkenazi Jewish (ASJ)

AF:

0.00452

AC:

AN:

15928

East Asian (EAS)

AF:

0.0000779

AC:

AN:

12844

South Asian (SAS)

AF:

0.00440

AC:

335

AN:

76104

European-Finnish (FIN)

AF:

0.000877

AC:

AN:

27378

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

4402

European-Non Finnish (NFE)

AF:

0.00432

AC:

3977

AN:

920720

Other (OTH)

AF:

0.00346

AC:

144

AN:

41638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

224

447

671

894

1118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.00316

AC:

481

AN:

152286

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

226

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41562

American (AMR)

AF:

0.00373

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00581

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00465

AC:

316

AN:

68024

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00380

Hom.:

Bravo

AF:

0.00372

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

-0.36

CADD

Benign

2.1

(source)

DANN

Benign

0.79

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism

(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