3-12516442-A-ATGTGTGTG

Variant names:

• chr3-12516442-A-ATGTGTGTG
• rs1491196550
• NM_025265.4:c.910-168_910-167insGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_025265.4(TSEN2):​c.910-168_910-167insGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0057 (3 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

Genes affected

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]

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00568 (506/89156) while in subpopulation NFE AF= 0.00848 (354/41766). AF 95% confidence interval is 0.00775. There are 3 homozygotes in gnomad4. There are 230 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-168_910-167insGTGTGTGT		intron_variant	Intron 6 of 11	ENST00000284995.11	NP_079541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN2	ENST00000284995.11	c.910-169_910-168insTGTGTGTG		intron_variant	Intron 6 of 11	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.00568 AC: 506 AN: 89078 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.00702

Gnomad EAS AF: 0.000712

Gnomad SAS AF: 0.00276

Gnomad FIN AF: 0.00317

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00847

Gnomad OTH AF: 0.00775

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

GnomAD4 genome AF: 0.00568 AC: 506 AN: 89156 Hom.: 3 Cov.: 0 AF XY: 0.00537 AC XY: 230 AN XY: 42812

Gnomad4 AFR AF: 0.00196

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00702

Gnomad4 EAS AF: 0.000712

Gnomad4 SAS AF: 0.00277

Gnomad4 FIN AF: 0.00317

Gnomad4 NFE AF: 0.00848

Gnomad4 OTH AF: 0.00768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1491196550; hg19: chr3-12557941;