12-40441116-C-T

Position:

• chr12-40441116-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3 BA1

The NM_173600.2(MUC19):​c.3677C>T​(p.Ser1226Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,303,634 control chromosomes in the GnomAD database, including 13,243 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 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 0.11 (1039 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12204 hom.)
• Consequence: MUC19 NM_173600.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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 -7 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.21
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC19	NM_173600.2	c.3677C>T	p.Ser1226Phe	missense_variant	31/172		NP_775871.2
LOC105369736	XR_007063562.1	n.74+2707G>A		intron_variant
LOC105369736	XR_944866.1	n.74+2707G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.3677C>T	p.Ser1226Phe	missense_variant	31/173	5		ENSP00000508949.1
ENSG00000258167	ENST00000552757.1	n.25+2707G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16033 AN: 151990 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.0991

GnomAD3 exomes AF: 0.103 AC: 15456 AN: 149492 Hom.: 1074 AF XY: 0.101 AC XY: 8143 AN XY: 80386

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.0637

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.0157

Gnomad SAS exome AF: 0.0404

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.139 AC: 160373 AN: 1151526 Hom.: 12204 Cov.: 30 AF XY: 0.136 AC XY: 76977 AN XY: 564640

Gnomad4 AFR exome AF: 0.0356

Gnomad4 AMR exome AF: 0.0638

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.0401

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.105 AC: 16037 AN: 152108 Hom.: 1039 Cov.: 32 AF XY: 0.104 AC XY: 7724 AN XY: 74360

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.0839

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.0981

Alfa AF: 0.135 Hom.: 2568

Bravo AF: 0.0980

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	22
DANN	Uncertain	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4768261; hg19: chr12-40834918;