3-12541569-A-G

Position:

• chr3-12541569-A-G

Variant summary

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

The NM_001195279.2(MKRN2OS):​c.431+291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,962 control chromosomes in the GnomAD database, including 12,521 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 0.39 (12521 hom., cov: 31)
• Consequence: MKRN2OS NM_001195279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKRN2OS	NM_001195279.2	c.431+291T>C		intron_variant		ENST00000564146.4	NP_001182208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKRN2OS	ENST00000564146.4	c.431+291T>C		intron_variant		5	NM_001195279.2	ENSP00000455385.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58661 AN: 151844 Hom.: 12499 Cov.: 31

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.386 AC: 58711 AN: 151962 Hom.: 12521 Cov.: 31 AF XY: 0.381 AC XY: 28321 AN XY: 74272

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0829

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.364

Alfa AF: 0.368 Hom.: 1329

Bravo AF: 0.393

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs2454431; hg19: chr3-12583068;