12-40518410-C-T

Position:

• chr12-40518410-C-T

Variant summary

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

The NM_173600.2(MUC19):​c.20231-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 154,944 control chromosomes in the GnomAD database, including 429 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 0.042 (429 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (0 hom.)
• Consequence: MUC19 NM_173600.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.862

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.20231-101C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.20285-101C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6317 AN: 152058 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.00723 AC: 20 AN: 2768 Hom.: 0 AF XY: 0.00907 AC XY: 13 AN XY: 1434

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00485

GnomAD4 genome AF: 0.0416 AC: 6329 AN: 152176 Hom.: 429 Cov.: 33 AF XY: 0.0397 AC XY: 2954 AN XY: 74396

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0325 Hom.: 45

Bravo AF: 0.0476

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17128396; hg19: chr12-40912212;