17-75517101-CGCCCTCCCTGCCCTCCCT-CGCCCTCCCTGCCCTCCCTGCCCTCCCTGCCCTCCCT

Variant names:

• chr17-75517101-C-CGCCCTCCCTGCCCTCCCT
• rs58038334
• NM_207346.3:c.285+39_286-33dupGCCCTCCCTGCCCTCCCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_207346.3(TSEN54):​c.285+39_286-33dupGCCCTCCCTGCCCTCCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,397,498 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: TSEN54 NM_207346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

Genes affected

TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]

TSEN54 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• pontocerebellar hypoplasia type 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• pontocerebellar hypoplasia type 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN54	NM_207346.3	c.285+39_286-33dupGCCCTCCCTGCCCTCCCT		intron_variant	Intron 3 of 10	ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11	c.285+39_286-33dupGCCCTCCCTGCCCTCCCT		intron_variant	Intron 3 of 10	1	NM_207346.3	ENSP00000327487.6

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1397498 Hom.: 0 Cov.: 34 AF XY: 0.00000289 AC XY: 2 AN XY: 691852

African (AFR) AF: 0.00 AC: 0 AN: 31934

American (AMR) AF: 0.0000512 AC: 2 AN: 39080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 37332

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1071658

Other (OTH) AF: 0.00 AC: 0 AN: 58066

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs58038334; hg19: chr17-73513182;