rs2900

Positions:

• chr15-23572574-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000568252.1(MKRN3):​c.305+6487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,128 control chromosomes in the GnomAD database, including 2,778 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 0.18 (2778 hom., cov: 33)
• Consequence: MKRN3 ENST00000568252.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

Genes affected

MKRN3 (HGNC:7114): (makorin ring finger protein 3) The protein encoded by this gene contains a RING (C3HC4) zinc finger motif and several C3H zinc finger motifs. This gene is intronless and imprinted, with expression only from the paternal allele. Disruption of the imprinting at this locus may contribute to Prader-Willi syndrome. An antisense RNA of unknown function has been found overlapping this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKRN3	ENST00000568252.1	c.305+6487G>A		intron_variant		1
MKRN3	ENST00000564592.2	c.483-2772G>A		intron_variant		3
MKRN3	ENST00000647595.1	c.51+6741G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27986 AN: 152010 Hom.: 2775 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 28003 AN: 152128 Hom.: 2778 Cov.: 33 AF XY: 0.188 AC XY: 13956 AN XY: 74368

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.187

Alfa AF: 0.158 Hom.: 2638

Bravo AF: 0.191

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2900; hg19: chr15-23817721;