12-40485730-G-A

Position:

• chr12-40485730-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000454784.10(MUC19):​c.12778G>A​(p.Asp4260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00803 in 944,066 control chromosomes in the GnomAD database, including 1,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (116 hom., cov: 33)
  • Exomes 𝑓: 0.0086 (1191 hom.)
• Consequence: MUC19 ENST00000454784.10 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-40485730-G-A is Benign according to our data. Variant chr12-40485730-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 116 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC19	NM_173600.2	c.12777G>A	p.Val4259Val	synonymous_variant	57/172		NP_775871.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC19	ENST00000454784.10	c.12778G>A	p.Asp4260Asn	missense_variant	56/173	5		ENSP00000508949.1

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 695 AN: 145526 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.00173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00613

Gnomad ASJ AF: 0.00584

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000673

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00772

Gnomad OTH AF: 0.00454

GnomAD4 exome AF: 0.00862 AC: 6886 AN: 798434 Hom.: 1191 Cov.: 39 AF XY: 0.00859 AC XY: 3169 AN XY: 368764

Gnomad4 AFR exome AF: 0.000789

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.00500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000639

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00910

Gnomad4 OTH exome AF: 0.00757

GnomAD4 genome AF: 0.00477 AC: 695 AN: 145632 Hom.: 116 Cov.: 33 AF XY: 0.00417 AC XY: 297 AN XY: 71160

Gnomad4 AFR AF: 0.00172

Gnomad4 AMR AF: 0.00612

Gnomad4 ASJ AF: 0.00584

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000673

Gnomad4 NFE AF: 0.00772

Gnomad4 OTH AF: 0.00449

Alfa AF: 0.00395 Hom.: 5

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

Oct 01, 2022

MUC19: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144308011; hg19: chr12-40879532;