3-12568438-G-A

Variant names:

• chr3-12568438-G-A
• rs2633442
• NM_014160.5:c.27-437G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014160.5(MKRN2):​c.27-437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,090 control chromosomes in the GnomAD database, including 14,773 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 0.43 (14773 hom., cov: 32)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014160.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2	NM_014160.5	MANE Select	c.27-437G>A		intron	N/A	NP_054879.3
	MKRN2	NM_001271707.2		c.27-1633G>A		intron	N/A	NP_001258636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2	ENST00000170447.12	TSL:1 MANE Select	c.27-437G>A		intron	N/A	ENSP00000170447.7
	MKRN2	ENST00000677142.1		c.60-437G>A		intron	N/A	ENSP00000504455.1
	MKRN2	ENST00000448482.1	TSL:5	c.27-437G>A		intron	N/A	ENSP00000397983.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65348 AN: 151972 Hom.: 14754 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.430 AC: 65393 AN: 152090 Hom.: 14773 Cov.: 32 AF XY: 0.422 AC XY: 31379 AN XY: 74352

African (AFR) AF: 0.532 AC: 22065 AN: 41444

American (AMR) AF: 0.351 AC: 5366 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3472

East Asian (EAS) AF: 0.0816 AC: 423 AN: 5186

South Asian (SAS) AF: 0.171 AC: 823 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4574 AN: 10578

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29386 AN: 67978

Other (OTH) AF: 0.426 AC: 899 AN: 2112

Alfa AF: 0.427 Hom.: 7304

Bravo AF: 0.430

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2633442; hg19: chr3-12609937;