chr3-12568438-G-A

Position:

• chr3-12568438-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKRN2	NM_014160.5	c.27-437G>A		intron_variant		ENST00000170447.12
MKRN2	NM_001271707.2	c.27-1633G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKRN2	ENST00000170447.12	c.27-437G>A		intron_variant		1	NM_014160.5	P1

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

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.0816

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.426

Alfa AF: 0.422 Hom.: 6031

Bravo AF: 0.430

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.56

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: rs2633442; hg19: chr3-12609937;