rs753601501

Variant names:

• chr3-12568994-C-G
• rs753601501
• NM_014160.5:c.146C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-12568994-C-G
• chr3-12568994-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014160.5(MKRN2):​c.146C>G​(p.Thr49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MKRN2 NM_014160.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

ACMG classification

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=0.09625006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKRN2	NM_014160.5	c.146C>G	p.Thr49Ser	missense_variant	Exon 2 of 8	ENST00000170447.12	NP_054879.3
MKRN2	NM_001271707.2	c.27-1077C>G		intron_variant	Intron 1 of 6		NP_001258636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12	c.146C>G	p.Thr49Ser	missense_variant	Exon 2 of 8	1	NM_014160.5	ENSP00000170447.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251106 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135716

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461646 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727130

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.038	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.42	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.42	N;N
REVEL	Benign	0.14
Sift	Benign	0.11	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0020	B;B
Vest4		0.11
MutPred		0.41		Gain of glycosylation at T49 (P = 0.0072);Gain of glycosylation at T49 (P = 0.0072);
MVP		0.43
MPC		0.18
ClinPred		0.16	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs753601501; hg19: chr3-12610493;