NM_025265.4:c.910-124_910-123dupTG

Variant names:

• chr3-12516446-A-ATG
• rs68107346
• NM_025265.4:c.910-124_910-123dupTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_025265.4(TSEN2):​c.910-124_910-123dupTG 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 0.0022 (1 hom., cov: 0)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00224 (283/126546) while in subpopulation SAS AF= 0.00996 (43/4316). AF 95% confidence interval is 0.0076. There are 1 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN2	NM_025265.4	c.910-124_910-123dupTG		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.910-165_910-164insTG		intron_variant	Intron 6 of 11	1	NM_025265.4	ENSP00000284995.6

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 283 AN: 126458 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00103

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.000957

Gnomad OTH AF: 0.00226

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

GnomAD4 genome AF: 0.00224 AC: 283 AN: 126546 Hom.: 1 Cov.: 0 AF XY: 0.00243 AC XY: 149 AN XY: 61440

Gnomad4 AFR AF: 0.00343

Gnomad4 AMR AF: 0.00171

Gnomad4 ASJ AF: 0.00103

Gnomad4 EAS AF: 0.00832

Gnomad4 SAS AF: 0.00996

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000957

Gnomad4 OTH AF: 0.00223

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;