chr12-40429552-G-C

Variant names:

• chr12-40429552-G-C
• rs11564245
• ENST00000454784.10:c.2407G>C

Variant summary

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

The NM_173600.2(MUC19):​c.2407G>C​(p.Asp803His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,283,110 control chromosomes in the GnomAD database, including 10,100 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 0.095 (1011 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9089 hom.)
• Consequence: MUC19 NM_173600.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 13 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]

ENSG00000258167 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.1).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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.2407G>C	p.Asp803His	missense	Exon 21 of 172	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	ENST00000454784.10	TSL:5	c.2407G>C	p.Asp803His	missense	Exon 21 of 173	ENSP00000508949.1
	ENSG00000258167	ENST00000552757.2	TSL:5	n.66-9241C>G		intron	N/A
	ENSG00000258167	ENST00000724141.1		n.78-9241C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14460 AN: 152096 Hom.: 1011 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0845

GnomAD2 exomes AF: 0.103 AC: 13604 AN: 132220 AF XY: 0.0993

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.0679

Gnomad ASJ exome AF: 0.0891

Gnomad EAS exome AF: 0.0179

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.120 AC: 135563 AN: 1130896 Hom.: 9089 Cov.: 29 AF XY: 0.117 AC XY: 65036 AN XY: 554198

African (AFR) AF: 0.0204 AC: 472 AN: 23182

American (AMR) AF: 0.0673 AC: 1636 AN: 24318

Ashkenazi Jewish (ASJ) AF: 0.0886 AC: 1350 AN: 15232

East Asian (EAS) AF: 0.0181 AC: 208 AN: 11504

South Asian (SAS) AF: 0.0370 AC: 2689 AN: 72604

European-Finnish (FIN) AF: 0.238 AC: 6478 AN: 27208

Middle Eastern (MID) AF: 0.0812 AC: 349 AN: 4296

European-Non Finnish (NFE) AF: 0.129 AC: 117915 AN: 911694

Other (OTH) AF: 0.109 AC: 4466 AN: 40858

GnomAD4 genome AF: 0.0950 AC: 14458 AN: 152214 Hom.: 1011 Cov.: 32 AF XY: 0.0977 AC XY: 7269 AN XY: 74422

African (AFR) AF: 0.0260 AC: 1079 AN: 41542

American (AMR) AF: 0.0735 AC: 1125 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5176

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4832

European-Finnish (FIN) AF: 0.247 AC: 2614 AN: 10570

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8681 AN: 68016

Other (OTH) AF: 0.0836 AC: 176 AN: 2106

Alfa AF: 0.111 Hom.: 355

Bravo AF: 0.0814

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.080
CADD	Benign	21
DANN	Uncertain	0.99
PhyloP100		2.5
Mutation Taster		=97/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11564245; hg19: chr12-40823354;