12-40408359-A-G

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.396A>G(p.Ser132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,278,358 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (2 hom.)
• Consequence: MUC19 NM_173600.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-40408359-A-G is Benign according to our data. Variant chr12-40408359-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC19	NM_173600.2	c.396A>G	p.Ser132=	synonymous_variant	5/172
LOC105369736	XR_944868.3	n.304+7942T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC19	ENST00000454784.10	c.396A>G	p.Ser132=	synonymous_variant	5/173	5		P1
	ENST00000552757.1	n.118-9695T>C		intron_variant, non_coding_transcript_variant		5
MUC19	ENST00000676020.2	n.449A>G		non_coding_transcript_exon_variant	5/15

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00131 AC: 160 AN: 122422 Hom.: 0 AF XY: 0.00121 AC XY: 81 AN XY: 67142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000973

Gnomad ASJ exome AF: 0.0137

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000283

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000437

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000409 AC: 461 AN: 1126048 Hom.: 2 Cov.: 31 AF XY: 0.000429 AC XY: 237 AN XY: 552434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000913

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000376

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74474

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00212 Hom.: 0

Bravo AF: 0.000642

Asia WGS AF: 0.000577 AC: 2 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

Jun 01, 2022

MUC19: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.7
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143082493; hg19: chr12-40802161;