dbSNP rs9855183: MKRN2:c.968+22C>T (chr3-12576763-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014160.5(MKRN2):c.968+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,523,290 control chromosomes in the GnomAD database, including 12,820 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 0.17 ( 3566 hom., cov: 29)

Exomes 𝑓: 0.10 ( 9254 hom. )

Consequence

MKRN2
NM_014160.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Publications

10 publications found

Variant links:

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]

MKRN2 links:

Metazoa_SRP (HGNC:):

Metazoa_SRP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKRN2	NM_014160.5 link	c.968+22C>T		intron_variant	Intron 6 of 7	ENST00000170447.12	NP_054879.3
MKRN2	NM_001271707.2 link	c.839+22C>T		intron_variant	Intron 5 of 6		NP_001258636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12 link	c.968+22C>T		intron_variant	Intron 6 of 7	1	NM_014160.5	ENSP00000170447.7		Q9H000-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26281

AN:

151306

Hom.:

3556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0925

Gnomad ASJ

AF:

0.0777

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.0705

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0982

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.105

AC:

26090

AN:

249324

AF XY:

0.0999

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.0586

Gnomad ASJ exome

AF:

0.0824

Gnomad EAS exome

AF:

0.0241

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.0965

Gnomad OTH exome

AF:

0.0955

GnomAD4 exome

AF:

0.104

AC:

142519

AN:

1371866

Hom.:

9254

Cov.:

AF XY:

0.102

AC XY:

70279

AN XY:

686378

show subpopulations

African (AFR)

AF:

0.395

AC:

12456

AN:

31506

American (AMR)

AF:

0.0607

AC:

2684

AN:

44250

Ashkenazi Jewish (ASJ)

AF:

0.0817

AC:

2066

AN:

25276

East Asian (EAS)

AF:

0.0318

AC:

1237

AN:

38850

South Asian (SAS)

AF:

0.0724

AC:

6083

AN:

84014

European-Finnish (FIN)

AF:

0.136

AC:

7173

AN:

52796

Middle Eastern (MID)

AF:

0.107

AC:

596

AN:

5546

European-Non Finnish (NFE)

AF:

0.101

AC:

103816

AN:

1032574

Other (OTH)

AF:

0.112

AC:

6408

AN:

57054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5827

11655

17482

23310

29137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3808

7616

11424

15232

19040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26315

AN:

151424

Hom.:

3566

Cov.:

AF XY:

0.172

AC XY:

12697

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.380

AC:

15618

AN:

41092

American (AMR)

AF:

0.0923

AC:

1404

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.0777

AC:

269

AN:

3464

East Asian (EAS)

AF:

0.0229

AC:

118

AN:

5142

South Asian (SAS)

AF:

0.0693

AC:

333

AN:

4804

European-Finnish (FIN)

AF:

0.139

AC:

1458

AN:

10488

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0982

AC:

6667

AN:

67916

Other (OTH)

AF:

0.134

AC:

282

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

904

1808

2711

3615

4519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.118

Hom.:

2744

Bravo

AF:

0.180

Asia WGS

AF:

0.0720

AC:

255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.68

(source)

DANN

Benign

0.80

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over