rs2933353

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173600.2(MUC19):ā€‹c.5285A>Cā€‹(p.Glu1762Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,303,668 control chromosomes in the GnomAD database, including 361,289 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.70 ( 38230 hom., cov: 31)
Exomes š‘“: 0.75 ( 323059 hom. )

Consequence

MUC19
NM_173600.2 missense

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.09).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUC19NM_173600.2 linkuse as main transcriptc.5285A>C p.Glu1762Ala missense_variant 47/172 NP_775871.2 Q7Z5P9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUC19ENST00000454784.10 linkuse as main transcriptc.5285A>C p.Glu1762Ala missense_variant 47/1735 ENSP00000508949.1

Frequencies

GnomAD3 genomes
AF:
0.704
AC:
106894
AN:
151836
Hom.:
38197
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.568
Gnomad AMI
AF:
0.677
Gnomad AMR
AF:
0.773
Gnomad ASJ
AF:
0.772
Gnomad EAS
AF:
0.675
Gnomad SAS
AF:
0.842
Gnomad FIN
AF:
0.761
Gnomad MID
AF:
0.753
Gnomad NFE
AF:
0.751
Gnomad OTH
AF:
0.725
GnomAD3 exomes
AF:
0.758
AC:
112635
AN:
148642
Hom.:
42977
AF XY:
0.764
AC XY:
61137
AN XY:
80038
show subpopulations
Gnomad AFR exome
AF:
0.561
Gnomad AMR exome
AF:
0.797
Gnomad ASJ exome
AF:
0.783
Gnomad EAS exome
AF:
0.663
Gnomad SAS exome
AF:
0.826
Gnomad FIN exome
AF:
0.764
Gnomad NFE exome
AF:
0.749
Gnomad OTH exome
AF:
0.760
GnomAD4 exome
AF:
0.748
AC:
861076
AN:
1151714
Hom.:
323059
Cov.:
45
AF XY:
0.751
AC XY:
424039
AN XY:
564764
show subpopulations
Gnomad4 AFR exome
AF:
0.563
Gnomad4 AMR exome
AF:
0.796
Gnomad4 ASJ exome
AF:
0.781
Gnomad4 EAS exome
AF:
0.666
Gnomad4 SAS exome
AF:
0.825
Gnomad4 FIN exome
AF:
0.763
Gnomad4 NFE exome
AF:
0.745
Gnomad4 OTH exome
AF:
0.739
GnomAD4 genome
AF:
0.704
AC:
106977
AN:
151954
Hom.:
38230
Cov.:
31
AF XY:
0.709
AC XY:
52672
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.568
Gnomad4 AMR
AF:
0.773
Gnomad4 ASJ
AF:
0.772
Gnomad4 EAS
AF:
0.674
Gnomad4 SAS
AF:
0.842
Gnomad4 FIN
AF:
0.761
Gnomad4 NFE
AF:
0.751
Gnomad4 OTH
AF:
0.727
Alfa
AF:
0.742
Hom.:
90374
Bravo
AF:
0.695
Asia WGS
AF:
0.724
AC:
2519
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.1
CADD
Benign
1.6
DANN
Benign
0.078

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2933353; hg19: chr12-40857943; API