ENST00000454784.10:c.5285A>C

Variant names:

• chr12-40464141-A-C
• rs2933353
• ENST00000454784.10:c.5285A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000454784.10(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. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38230 hom., cov: 31)
  • Exomes 𝑓: 0.75 (323059 hom.)
• Consequence: MUC19 ENST00000454784.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.018).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.82 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	NM_173600.2		c.5285A>C	p.Glu1762Ala	missense	Exon 47 of 172	NP_775871.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	ENST00000454784.10	TSL:5	c.5285A>C	p.Glu1762Ala	missense	Exon 47 of 173	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

GnomAD2 exomes AF: 0.758 AC: 112635 AN: 148642 AF XY: 0.764

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 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

African (AFR) AF: 0.563 AC: 13730 AN: 24408

American (AMR) AF: 0.796 AC: 22501 AN: 28256

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 12454 AN: 15938

East Asian (EAS) AF: 0.666 AC: 8546 AN: 12838

South Asian (SAS) AF: 0.825 AC: 62883 AN: 76188

European-Finnish (FIN) AF: 0.763 AC: 20854 AN: 27340

Middle Eastern (MID) AF: 0.751 AC: 3304 AN: 4398

European-Non Finnish (NFE) AF: 0.745 AC: 686028 AN: 920730

Other (OTH) AF: 0.739 AC: 30776 AN: 41618

GnomAD4 genome AF: 0.704 AC: 106977 AN: 151954 Hom.: 38230 Cov.: 31 AF XY: 0.709 AC XY: 52672 AN XY: 74286

African (AFR) AF: 0.568 AC: 23535 AN: 41422

American (AMR) AF: 0.773 AC: 11783 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2675 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3478 AN: 5160

South Asian (SAS) AF: 0.842 AC: 4044 AN: 4804

European-Finnish (FIN) AF: 0.761 AC: 8035 AN: 10564

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51054 AN: 67978

Other (OTH) AF: 0.727 AC: 1533 AN: 2110

Alfa AF: 0.733 Hom.: 133893

Bravo AF: 0.695

Asia WGS AF: 0.724 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.078
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2933353; hg19: chr12-40857943;