rs2933353

Positions:

• chr12-40464141-A-C
• chr12-40464141-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173600.2(MUC19):​c.5285A>C​(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: 𝑓 0.70 (38230 hom., cov: 31)
  • Exomes 𝑓: 0.75 (323059 hom.)
• Consequence: MUC19 NM_173600.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

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
MUC19	NM_173600.2	c.5285A>C	p.Glu1762Ala	missense_variant	47/172		NP_775871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.5285A>C	p.Glu1762Ala	missense_variant	47/173	5		ENSP00000508949.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106894 AN: 151836 Hom.: 38197 Cov.: 31

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

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

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

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

Other links and lift over

dbSNP: rs2933353; hg19: chr12-40857943;