12-40465588-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_173600.2(MUC19):c.5634T>C(p.Gly1878=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,261,892 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (3 hom.)
• Consequence: MUC19 NM_173600.2 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-40465588-T-C is Benign according to our data. Variant chr12-40465588-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.036 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.5634T>C	p.Gly1878=	splice_region_variant, synonymous_variant	50/172

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.5634T>C	p.Gly1878=	splice_region_variant, synonymous_variant	50/173	5		P1

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000950 AC: 102 AN: 107392 Hom.: 0 AF XY: 0.000952 AC XY: 55 AN XY: 57768

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.000208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000611

Gnomad FIN exome AF: 0.00373

Gnomad NFE exome AF: 0.000875

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000787 AC: 873 AN: 1109642 Hom.: 3 Cov.: 30 AF XY: 0.000721 AC XY: 391 AN XY: 541954

Gnomad4 AFR exome AF: 0.000134

Gnomad4 AMR exome AF: 0.000154

Gnomad4 ASJ exome AF: 0.000462

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000714

Gnomad4 FIN exome AF: 0.00333

Gnomad4 NFE exome AF: 0.000769

Gnomad4 OTH exome AF: 0.000655

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.00107 AC XY: 80 AN XY: 74452

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.000450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

MUC19: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.92
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs531019133; hg19: chr12-40859390;