3-12576497-G-A

Variant names:

• chr3-12576497-G-A
• rs1542848
• NM_014160.5:c.858-134G>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.858-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 579,740 control chromosomes in the GnomAD database, including 38,895 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 0.39 (11907 hom., cov: 30)
  • Exomes 𝑓: 0.34 (26988 hom.)
• Consequence: MKRN2 NM_014160.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 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.858-134G>A		intron	N/A	NP_054879.3
	MKRN2	NM_001271707.2		c.729-134G>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.858-134G>A		intron	N/A	ENSP00000170447.7
	MKRN2	ENST00000676544.1		n.2442G>A		non_coding_transcript_exon	Exon 5 of 7
	MKRN2	ENST00000677142.1		c.891-134G>A		intron	N/A	ENSP00000504455.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58477 AN: 151764 Hom.: 11895 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.338 AC: 144766 AN: 427858 Hom.: 26988 AF XY: 0.329 AC XY: 74480 AN XY: 226572

African (AFR) AF: 0.486 AC: 5132 AN: 10564

American (AMR) AF: 0.256 AC: 4331 AN: 16912

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 4304 AN: 11678

East Asian (EAS) AF: 0.0947 AC: 2509 AN: 26506

South Asian (SAS) AF: 0.167 AC: 6930 AN: 41538

European-Finnish (FIN) AF: 0.376 AC: 14458 AN: 38422

Middle Eastern (MID) AF: 0.327 AC: 1078 AN: 3294

European-Non Finnish (NFE) AF: 0.382 AC: 97772 AN: 255770

Other (OTH) AF: 0.356 AC: 8252 AN: 23174

GnomAD4 genome AF: 0.385 AC: 58514 AN: 151882 Hom.: 11907 Cov.: 30 AF XY: 0.378 AC XY: 28026 AN XY: 74226

African (AFR) AF: 0.488 AC: 20176 AN: 41380

American (AMR) AF: 0.302 AC: 4608 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.0819 AC: 424 AN: 5180

South Asian (SAS) AF: 0.159 AC: 767 AN: 4814

European-Finnish (FIN) AF: 0.381 AC: 4006 AN: 10528

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26092 AN: 67960

Other (OTH) AF: 0.383 AC: 809 AN: 2112

Alfa AF: 0.357 Hom.: 3858

Bravo AF: 0.384

Asia WGS AF: 0.158 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.78
PhyloP100		-0.37
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: rs1542848; hg19: chr3-12617996;