3-12582191-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014160.5(MKRN2):​c.1189G>T​(p.Asp397Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MKRN2
NM_014160.5 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.11
Variant links:
Genes affected
MKRN2 (HGNC:7113): (makorin ring finger protein 2) This gene encodes a probable E3 ubiquitin ligase containing several zinc finger domains, that is a member of the makorin RING zinc-finger protein family. This gene overlaps the v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) gene in an antisense orientation and may have a co-regulatory function with RAF1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
RAF1 (HGNC:9829): (Raf-1 proto-oncogene, serine/threonine kinase) This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MKRN2NM_014160.5 linkc.1189G>T p.Asp397Tyr missense_variant Exon 8 of 8 ENST00000170447.12 NP_054879.3
MKRN2NM_001271707.2 linkc.1060G>T p.Asp354Tyr missense_variant Exon 7 of 7 NP_001258636.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MKRN2ENST00000170447.12 linkc.1189G>T p.Asp397Tyr missense_variant Exon 8 of 8 1 NM_014160.5 ENSP00000170447.7 Q9H000-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251328
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Uncertain
0.052
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;.;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.2
M;.;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-2.3
N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0080
D;D;D
Sift4G
Uncertain
0.015
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.54
MutPred
0.26
Loss of disorder (P = 0.0053);.;.;
MVP
0.50
MPC
0.85
ClinPred
0.92
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.63

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: rs554403152; hg19: chr3-12623690; API