chr12-40441116-C-A

Position:

• chr12-40441116-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173600.2(MUC19):​c.3677C>A​(p.Ser1226Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S1226F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• 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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.14

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC19	NM_173600.2	c.3677C>A	p.Ser1226Tyr	missense_variant	31/172		NP_775871.2
LOC105369736	XR_944868.3	n.74+2707G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.3677C>A	p.Ser1226Tyr	missense_variant	31/173	5		ENSP00000508949	P1
	ENST00000552757.1	n.25+2707G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	21
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;