12-40480581-T-C

Position:

• chr12-40480581-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173600.2(MUC19):​c.7629T>C​(p.Asp2543=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 985,260 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0088 (34 hom.)
• Consequence: MUC19 NM_173600.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.49

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-40480581-T-C is Benign according to our data. Variant chr12-40480581-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.7629T>C	p.Asp2543=	synonymous_variant	56/172

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.7629T>C	p.Asp2543=	synonymous_variant	56/173	5		P1

Frequencies

GnomAD3 genomes AF: 0.00572 AC: 870 AN: 152034 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00884 AC: 7367 AN: 833108 Hom.: 34 Cov.: 32 AF XY: 0.00869 AC XY: 3345 AN XY: 384714

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.0256

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00389

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.00908

Gnomad4 OTH exome AF: 0.00821

GnomAD4 genome AF: 0.00571 AC: 869 AN: 152152 Hom.: 3 Cov.: 34 AF XY: 0.00503 AC XY: 374 AN XY: 74398

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00863

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00762 Hom.: 1

Bravo AF: 0.00563

Asia WGS AF: 0.00260 AC: 10 AN: 3478

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

Feb 01, 2023

MUC19: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149170137; hg19: chr12-40874383;