12-40441116-C-T

Variant names:

• chr12-40441116-C-T
• rs4768261
• ENST00000454784.10:c.3677C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 10 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.3677C>T	p.Ser1226Phe	missense	Exon 31 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.3677C>T	p.Ser1226Phe	missense	Exon 31 of 173	ENSP00000508949.1
	ENSG00000258167	ENST00000552757.2	TSL:5	n.65+2707G>A		intron	N/A
	ENSG00000258167	ENST00000724141.1		n.77+2707G>A		intron	N/A

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

GnomAD2 exomes AF: 0.103 AC: 15456 AN: 149492 AF XY: 0.101

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 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

African (AFR) AF: 0.0356 AC: 868 AN: 24416

American (AMR) AF: 0.0638 AC: 1802 AN: 28236

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 1814 AN: 15930

East Asian (EAS) AF: 0.0157 AC: 202 AN: 12842

South Asian (SAS) AF: 0.0401 AC: 3051 AN: 76112

European-Finnish (FIN) AF: 0.172 AC: 4694 AN: 27324

Middle Eastern (MID) AF: 0.0914 AC: 402 AN: 4400

European-Non Finnish (NFE) AF: 0.155 AC: 142439 AN: 920646

Other (OTH) AF: 0.123 AC: 5101 AN: 41620

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

African (AFR) AF: 0.0414 AC: 1718 AN: 41508

American (AMR) AF: 0.0839 AC: 1283 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3470

East Asian (EAS) AF: 0.0156 AC: 81 AN: 5178

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4820

European-Finnish (FIN) AF: 0.171 AC: 1800 AN: 10544

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10194 AN: 67988

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.133 Hom.: 2989

Bravo AF: 0.0980

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	22
DANN	Uncertain	1.0
PhyloP100		0.67
Mutation Taster		=94/6	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4768261; hg19: chr12-40834918;