3-12576497-G-C

Variant names:

• chr3-12576497-G-C
• rs1542848
• NM_014160.5:c.858-134G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014160.5(MKRN2):​c.858-134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 429,314 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000023 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>C		intron	N/A	NP_054879.3
	MKRN2	NM_001271707.2		c.729-134G>C		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>C		intron	N/A	ENSP00000170447.7
	MKRN2	ENST00000676544.1		n.2442G>C		non_coding_transcript_exon	Exon 5 of 7
	MKRN2	ENST00000677142.1		c.891-134G>C		intron	N/A	ENSP00000504455.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000233 AC: 1 AN: 429314 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 227354

African (AFR) AF: 0.00 AC: 0 AN: 10608

American (AMR) AF: 0.00 AC: 0 AN: 16982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11722

East Asian (EAS) AF: 0.00 AC: 0 AN: 26538

South Asian (SAS) AF: 0.00 AC: 0 AN: 41636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3296

European-Non Finnish (NFE) AF: 0.00000389 AC: 1 AN: 256740

Other (OTH) AF: 0.00 AC: 0 AN: 23252

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 3858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		-0.37

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;