chr3-12574485-T-C

Variant names:

• chr3-12574485-T-C
• rs713178
• NM_014160.5:c.643-307T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2	NM_014160.5	MANE Select	c.643-307T>C		intron	N/A	NP_054879.3
	MKRN2	NM_001271707.2		c.514-307T>C		intron	N/A	NP_001258636.1	Q9H000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN2	ENST00000170447.12	TSL:1 MANE Select	c.643-307T>C		intron	N/A	ENSP00000170447.7	Q9H000-1
	MKRN2	ENST00000900946.1		c.964-307T>C		intron	N/A	ENSP00000571005.1
	MKRN2	ENST00000900947.1		c.724-307T>C		intron	N/A	ENSP00000571006.1

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

African (AFR) AF: 0.168 AC: 6958 AN: 41518

American (AMR) AF: 0.311 AC: 4753 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.0508 AC: 264 AN: 5192

South Asian (SAS) AF: 0.141 AC: 680 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2125 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16855 AN: 67954

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.237 Hom.: 8387

Bravo AF: 0.227

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.61
PhyloP100		-0.31
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: rs713178; hg19: chr3-12615984;