chr3-12516446-ATGTGTGTGTGTGTGTG-A

Variant names:

• chr3-12516446-ATGTGTGTGTGTGTGTG-A
• rs68107346
• NM_025265.4:c.910-138_910-123delTGTGTGTGTGTGTGTG

Variant summary

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

The NM_025265.4(TSEN2):​c.910-138_910-123delTGTGTGTGTGTGTGTG 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 0.019 (41 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779

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 amr. gnomad4 allele frequency = 0.0187 (2366/126550) while in subpopulation AMR AF= 0.0496 (665/13416). AF 95% confidence interval is 0.0464. There are 41 homozygotes in gnomad4. There are 1234 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-138_910-123delTGTGTGTGTGTGTGTG		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.910-164_910-149delTGTGTGTGTGTGTGTG		intron_variant	Intron 6 of 11	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2361 AN: 126462 Hom.: 40 Cov.: 0

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.00309

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0187 AC: 2366 AN: 126550 Hom.: 41 Cov.: 0 AF XY: 0.0201 AC XY: 1234 AN XY: 61442

Gnomad4 AFR AF: 0.00820

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.00309

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0379

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: rs68107346; hg19: chr3-12557945;