chr17-75517702-A-T

Variant names:

• chr17-75517702-A-T
• rs201404842
• NM_207346.3:c.468+47A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_207346.3(TSEN54):​c.468+47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,505,300 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: TSEN54 NM_207346.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.277
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-75517702-A-T is Benign according to our data. Variant chr17-75517702-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 263294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	NM_207346.3	MANE Select	c.468+47A>T		intron	N/A	NP_997229.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.468+47A>T		intron	N/A	ENSP00000327487.6
	TSEN54	ENST00000680999.1		c.468+47A>T		intron	N/A	ENSP00000504984.1
	TSEN54	ENST00000545228.3	TSL:5	c.468+47A>T		intron	N/A	ENSP00000438169.3

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000483 AC: 120 AN: 248606 AF XY: 0.000445

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000991

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.00116 AC: 1576 AN: 1352992 Hom.: 2 Cov.: 22 AF XY: 0.00113 AC XY: 764 AN XY: 679036

African (AFR) AF: 0.000192 AC: 6 AN: 31174

American (AMR) AF: 0.000269 AC: 12 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 39218

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84152

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50292

Middle Eastern (MID) AF: 0.000359 AC: 2 AN: 5566

European-Non Finnish (NFE) AF: 0.00148 AC: 1501 AN: 1015718

Other (OTH) AF: 0.000932 AC: 53 AN: 56840

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000550 AC XY: 41 AN XY: 74488

African (AFR) AF: 0.000337 AC: 14 AN: 41558

American (AMR) AF: 0.000458 AC: 7 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000377 Hom.: 0

Bravo AF: 0.000635

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201404842; hg19: chr17-73513783;