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12-40441144-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_173600.2(MUC19):c.3705C>T(p.Asp1235=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,303,966 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

MUC19
NM_173600.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.691
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-40441144-C-T is Benign according to our data. Variant chr12-40441144-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642861.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.691 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MUC19NM_173600.2 linkuse as main transcriptc.3705C>T p.Asp1235= synonymous_variant 31/172
LOC105369736XR_944868.3 linkuse as main transcriptn.74+2679G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MUC19ENST00000454784.10 linkuse as main transcriptc.3705C>T p.Asp1235= synonymous_variant 31/1735 P1
ENST00000552757.1 linkuse as main transcriptn.25+2679G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00317
AC:
482
AN:
152168
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00580
Gnomad FIN
AF:
0.00141
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00466
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00322
AC:
483
AN:
149898
Hom.:
3
AF XY:
0.00321
AC XY:
258
AN XY:
80486
show subpopulations
Gnomad AFR exome
AF:
0.00130
Gnomad AMR exome
AF:
0.00195
Gnomad ASJ exome
AF:
0.00393
Gnomad EAS exome
AF:
0.0000927
Gnomad SAS exome
AF:
0.00391
Gnomad FIN exome
AF:
0.000890
Gnomad NFE exome
AF:
0.00481
Gnomad OTH exome
AF:
0.00507
GnomAD4 exome
AF:
0.00408
AC:
4701
AN:
1151680
Hom.:
20
Cov.:
30
AF XY:
0.00407
AC XY:
2299
AN XY:
564676
show subpopulations
Gnomad4 AFR exome
AF:
0.00123
Gnomad4 AMR exome
AF:
0.00223
Gnomad4 ASJ exome
AF:
0.00452
Gnomad4 EAS exome
AF:
0.0000779
Gnomad4 SAS exome
AF:
0.00440
Gnomad4 FIN exome
AF:
0.000877
Gnomad4 NFE exome
AF:
0.00432
Gnomad4 OTH exome
AF:
0.00346
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00316
AC:
481
AN:
152286
Hom.:
1
Cov.:
32
AF XY:
0.00303
AC XY:
226
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00581
Gnomad4 FIN
AF:
0.00141
Gnomad4 NFE
AF:
0.00465
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00380
Hom.:
0
Bravo
AF:
0.00372
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023MUC19: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
2.1
Dann
Benign
0.79

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs151020006; hg19: chr12-40834946; API