12-40429552-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC19	NM_173600.2	c.2407G>C	p.Asp803His	missense_variant	Exon 21 of 172		NP_775871.2
LOC105369736	XR_007063562.1	n.75-9241C>G		intron_variant	Intron 1 of 4
LOC105369736	XR_944866.1	n.75-9241C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.2407G>C	p.Asp803His	missense_variant	Exon 21 of 173	5		ENSP00000508949.1
ENSG00000258167	ENST00000552757.1	n.26-9241C>G		intron_variant	Intron 1 of 3	5

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

GnomAD3 exomes AF: 0.103 AC: 13604 AN: 132220 Hom.: 1001 AF XY: 0.0993 AC XY: 7064 AN XY: 71132

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 SAS exome AF: 0.0381

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

Gnomad4 AFR exome AF: 0.0204

Gnomad4 AMR exome AF: 0.0673

Gnomad4 ASJ exome AF: 0.0886

Gnomad4 EAS exome AF: 0.0181

Gnomad4 SAS exome AF: 0.0370

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.109

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

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0836

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.080
CADD	Benign	21
DANN	Uncertain	0.99

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11564245; hg19: chr12-40823354;