rs9855183

chr3-12576763-C-T

Variant summary

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

The NM_014160.5(MKRN2):c.968+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,523,290 control chromosomes in the GnomAD database, including 12,820 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 0.17 (3566 hom., cov: 29)
  • Exomes 𝑓: 0.10 (9254 hom.)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKRN2	NM_014160.5	c.968+22C>T		intron_variant		ENST00000170447.12
MKRN2	NM_001271707.2	c.839+22C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKRN2	ENST00000170447.12	c.968+22C>T		intron_variant		1	NM_014160.5	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26281 AN: 151306 Hom.: 3556 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0777

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.105 AC: 26090 AN: 249324 Hom.: 2163 AF XY: 0.0999 AC XY: 13473 AN XY: 134800

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.0586

Gnomad ASJ exome AF: 0.0824

Gnomad EAS exome AF: 0.0241

Gnomad SAS exome AF: 0.0710

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.0965

Gnomad OTH exome AF: 0.0955

GnomAD4 exome AF: 0.104 AC: 142519 AN: 1371866 Hom.: 9254 Cov.: 22 AF XY: 0.102 AC XY: 70279 AN XY: 686378

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.0607

Gnomad4 ASJ exome AF: 0.0817

Gnomad4 EAS exome AF: 0.0318

Gnomad4 SAS exome AF: 0.0724

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.174 AC: 26315 AN: 151424 Hom.: 3566 Cov.: 29 AF XY: 0.172 AC XY: 12697 AN XY: 73972

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0777

Gnomad4 EAS AF: 0.0229

Gnomad4 SAS AF: 0.0693

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0982

Gnomad4 OTH AF: 0.134

Alfa AF: 0.111 Hom.: 1731

Bravo AF: 0.180

Asia WGS AF: 0.0720 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.68
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9855183; hg19: chr3-12618262;