Variant 12-40465588-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0360

Variant links:

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]

MUC19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.000952

AC XY:

AN XY:

57768

show subpopulations

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.:

Cov.:

AF XY:

0.000721

AC XY:

391

AN XY:

541954

show subpopulations

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.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74452

show subpopulations

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.:

Bravo

AF:

0.000450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over