rs2900

Variant names:

• chr15-23572574-G-A
• rs2900
• ENST00000568252.1:c.305+6487G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-23572574-G-A
• chr15-23572574-G-C
• chr15-23572574-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

MKRN3 Gene-Disease associations (from GenCC):

• precocious puberty, central, 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000568252.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKRN3	ENST00000568252.1	TSL:1	c.305+6487G>A		intron	N/A	ENSP00000456779.1	Q6NSB6
	MKRN3	ENST00000676568.1		c.927+5865G>A		intron	N/A	ENSP00000502884.1	A0A7I2YQ72
	MKRN3	ENST00000564592.2	TSL:3	c.483-2772G>A		intron	N/A	ENSP00000455368.1	H3BPL3

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

African (AFR) AF: 0.202 AC: 8367 AN: 41494

American (AMR) AF: 0.238 AC: 3640 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5176

South Asian (SAS) AF: 0.129 AC: 624 AN: 4828

European-Finnish (FIN) AF: 0.170 AC: 1800 AN: 10562

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10677 AN: 67998

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.166 Hom.: 4669

Bravo AF: 0.191

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.47
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2900; hg19: chr15-23817721;