rs763195944
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 8P and 4B. PVS1_StrongPM2PP5_ModerateBS2
The NM_005664.4(MKRN3):c.482delC(p.Pro161ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,440 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
MKRN3
NM_005664.4 frameshift
NM_005664.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.492
Publications
12 publications found
Genes affected
MKRN3 (HGNC:7114): (makorin ring finger protein 3) The protein encoded by this gene contains a RING (C3HC4) zinc finger motif and several C3H zinc finger motifs. This gene is intronless and imprinted, with expression only from the paternal allele. Disruption of the imprinting at this locus may contribute to Prader-Willi syndrome. An antisense RNA of unknown function has been found overlapping this gene. [provided by RefSeq, Jul 2008]
MKRN3 Gene-Disease associations (from GenCC):
- precocious puberty, central, 2Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-23566257-GC-G is Pathogenic according to our data. Variant chr15-23566257-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 2431610.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005664.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MKRN3 | TSL:6 MANE Select | c.482delC | p.Pro161ArgfsTer10 | frameshift | Exon 1 of 1 | ENSP00000313881.3 | Q13064 | ||
| MKRN3 | TSL:1 | c.305+177delC | intron | N/A | ENSP00000456779.1 | Q6NSB6 | |||
| MKRN3 | c.482delC | p.Pro161ArgfsTer10 | frameshift | Exon 1 of 2 | ENSP00000502884.1 | A0A7I2YQ72 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000402 AC: 1AN: 248862 AF XY: 0.00000740 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
248862
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461440Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727020 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461440
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
727020
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52980
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1112006
Other (OTH)
AF:
AC:
1
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Precocious puberty, central, 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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