Genetic Variant MUC19:p.His4190Asp (chr12-40485520-C-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_173600.2(MUC19):c.12567C>G(p.Val4189Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC19
NM_173600.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.96

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 12-40485520-C-G is Benign according to our data. Variant chr12-40485520-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3770945.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.96 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173600.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	NM_173600.2		c.12567C>G	p.Val4189Val	synonymous	Exon 57 of 172	NP_775871.2	Q7Z5P9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC19	ENST00000454784.10	TSL:5	c.12568C>G	p.His4190Asp	missense	Exon 56 of 173	ENSP00000508949.1

Frequencies

GnomAD3 genomes

AF:

0.0000146

AC:

AN:

137346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000243

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

833030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

384684

African (AFR)

AF:

0.00

AC:

AN:

15786

American (AMR)

AF:

0.00

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5148

East Asian (EAS)

AF:

0.00

AC:

AN:

3632

South Asian (SAS)

AF:

0.00

AC:

AN:

16458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1616

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

761838

Other (OTH)

AF:

0.00

AC:

AN:

27290

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000146

AC:

AN:

137454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67170

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000272

AC:

AN:

36752

American (AMR)

AF:

0.00

AC:

AN:

13702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3178

East Asian (EAS)

AF:

0.00

AC:

AN:

4474

South Asian (SAS)

AF:

0.000243

AC:

AN:

4118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62886

Other (OTH)

AF:

0.00

AC:

AN:

1868

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000169

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0070

(source)

DANN

Benign

0.40

PhyloP100

-7.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over