chr7-140479256-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000255977.7(MKRN1):ā€‹c.89C>Gā€‹(p.Pro30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Synonymous variant affecting the same amino acid position (i.e. P30P) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

MKRN1
ENST00000255977.7 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524
Variant links:
Genes affected
MKRN1 (HGNC:7112): (makorin ring finger protein 1) This gene encodes a protein that belongs to a novel class of zinc finger proteins. The encoded protein functions as a transcriptional co-regulator, and as an E3 ubiquitin ligase that promotes the ubiquitination and proteasomal degradation of target proteins. The protein encoded by this gene is thought to regulate RNA polymerase II-catalyzed transcription. Substrates for this protein's E3 ubiquitin ligase activity include the capsid protein of the West Nile virus and the catalytic subunit of the telomerase ribonucleoprotein. This protein controls cell cycle arrest and apoptosis by regulating p21, a cell cycle regulator, and the tumor suppressor protein p53. Pseudogenes of this gene are present on chromosomes 1, 3, 9, 12 and 20, and on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14506614).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MKRN1NM_013446.4 linkuse as main transcriptc.89C>G p.Pro30Arg missense_variant 1/8 ENST00000255977.7 NP_038474.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MKRN1ENST00000255977.7 linkuse as main transcriptc.89C>G p.Pro30Arg missense_variant 1/81 NM_013446.4 ENSP00000255977.2 Q9UHC7-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151992
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151992
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74244
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 13, 2023The c.89C>G (p.P30R) alteration is located in exon 1 (coding exon 1) of the MKRN1 gene. This alteration results from a C to G substitution at nucleotide position 89, causing the proline (P) at amino acid position 30 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Benign
0.91
DEOGEN2
Benign
0.091
T;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.39
T;T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.20
N;N
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.025
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.067
B;.
Vest4
0.13
MutPred
0.41
Gain of methylation at P30 (P = 0.0353);Gain of methylation at P30 (P = 0.0353);
MVP
0.10
MPC
0.15
ClinPred
0.19
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs200911173; hg19: chr7-140179056; API