rs1492332

Positions:

• chr12-40464652-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173600.2(MUC19):​c.5425+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,094 control chromosomes in the GnomAD database, including 7,401 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 0.30 (7401 hom., cov: 32)
• Consequence: MUC19 NM_173600.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC19	NM_173600.2	c.5425+154G>A		intron_variant			NP_775871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.5425+154G>A		intron_variant		5		ENSP00000508949.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45886 AN: 151976 Hom.: 7393 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45920 AN: 152094 Hom.: 7401 Cov.: 32 AF XY: 0.308 AC XY: 22901 AN XY: 74354

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.300

Alfa AF: 0.342 Hom.: 4330

Bravo AF: 0.276

Asia WGS AF: 0.341 AC: 1182 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1492332; hg19: chr12-40858454;