Genetic Variant MUC19:p.Asn4240Asp (chr12-40485670-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173600.2(MUC19):c.12717A>G(p.Val4239Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 797,210 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

MUC19
NM_173600.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.23

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-40485670-A-G is Benign according to our data. Variant chr12-40485670-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3771104.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.23 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

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.12717A>G	p.Val4239Val	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.12718A>G	p.Asn4240Asp	missense	Exon 56 of 173	ENSP00000508949.1

Frequencies

GnomAD3 genomes

AF:

0.000195

AC:

AN:

117992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000181

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000899

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000426

AC:

AN:

797210

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

368168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15186

American (AMR)

AF:

0.00

AC:

AN:

938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4792

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

15604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1512

European-Non Finnish (NFE)

AF:

0.0000466

AC:

AN:

729230

Other (OTH)

AF:

0.00

AC:

AN:

26102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000195

AC:

AN:

118088

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

AN XY:

57968

show subpopulations

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

African (AFR)

AF:

0.000313

AC:

AN:

31988

American (AMR)

AF:

0.000180

AC:

AN:

11082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2536

East Asian (EAS)

AF:

0.00

AC:

AN:

4096

South Asian (SAS)

AF:

0.000900

AC:

AN:

3332

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

8942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.000131

AC:

AN:

53566

Other (OTH)

AF:

0.00

AC:

AN:

1604

⚠️ 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: 0.255

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

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

-0.89

CADD

Benign

0.16

(source)

DANN

Benign

0.11

PhyloP100

-5.2

Mutation Taster

=100/0

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over