rs713178

chr3-12574485-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014160.5(MKRN2):c.643-307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,166 control chromosomes in the GnomAD database, including 3,922 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3922 hom., cov: 33)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKRN2	NM_014160.5	c.643-307T>C		intron_variant		ENST00000170447.12
MKRN2	NM_001271707.2	c.514-307T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKRN2	ENST00000170447.12	c.643-307T>C		intron_variant		1	NM_014160.5	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33350 AN: 152048 Hom.: 3909 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33402 AN: 152166 Hom.: 3922 Cov.: 33 AF XY: 0.216 AC XY: 16058 AN XY: 74408

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.234

Alfa AF: 0.239 Hom.: 6146

Bravo AF: 0.227

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.96
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs713178; hg19: chr3-12615984;