12-40431657-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_173600.2(MUC19):c.2564G>A(p.Arg855His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,304,100 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: MUC19 NM_173600.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-40431657-G-A is Benign according to our data. Variant chr12-40431657-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.2564G>A	p.Arg855His	missense_variant	22/172
LOC105369736	XR_944868.3	n.75-11346C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.2564G>A	p.Arg855His	missense_variant	22/173	5		P1
	ENST00000552757.1	n.26-11346C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152110 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00248 AC: 372 AN: 150258 Hom.: 1 AF XY: 0.00228 AC XY: 184 AN XY: 80656

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00381

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000488

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.00206

Gnomad OTH exome AF: 0.00366

GnomAD4 exome AF: 0.00157 AC: 1809 AN: 1151872 Hom.: 5 Cov.: 29 AF XY: 0.00155 AC XY: 876 AN XY: 564788

Gnomad4 AFR exome AF: 0.000164

Gnomad4 AMR exome AF: 0.000177

Gnomad4 ASJ exome AF: 0.00370

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000407

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.00127

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152228 Hom.: 5 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74422

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.00313

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.00115 AC: 4 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: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	18
Dann	Uncertain	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144344916; hg19: chr12-40825459; COSMIC: COSV71244076;