chr3-12572134-G-A

Variant names:

• chr3-12572134-G-A
• rs372538092
• NM_014160.5:c.403G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014160.5(MKRN2):​c.403G>A​(p.Asp135Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MKRN2 NM_014160.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.094680846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKRN2	NM_014160.5	c.403G>A	p.Asp135Asn	missense_variant	Exon 4 of 8	ENST00000170447.12	NP_054879.3
MKRN2	NM_001271707.2	c.274G>A	p.Asp92Asn	missense_variant	Exon 3 of 7		NP_001258636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12	c.403G>A	p.Asp135Asn	missense_variant	Exon 4 of 8	1	NM_014160.5	ENSP00000170447.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000319 AC: 8 AN: 251072 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135724

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461798 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000564 Hom.: 0

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.99	D;.;D
Vest4		0.12
MutPred		0.18		Loss of glycosylation at P140 (P = 0.0172);.;.;
MVP		0.53
MPC		0.20
ClinPred		0.088	T
GERP RS		3.6
Varity_R		0.044
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs372538092; hg19: chr3-12613633;