17-75517101-CGCCCTCCCT-C

Position:

• chr17-75517101-CGCCCTCCCT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_207346.3(TSEN54):​c.286-41_286-33delGCCCTCCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,540,818 control chromosomes in the GnomAD database, including 19,205 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4677 hom., cov: 27)
  • Exomes 𝑓: 0.14 (14528 hom.)
• Consequence: TSEN54 NM_207346.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-75517101-CGCCCTCCCT-C is Benign according to our data. Variant chr17-75517101-CGCCCTCCCT-C is described in ClinVar as [Benign]. Clinvar id is 263293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3	c.286-41_286-33delGCCCTCCCT		intron_variant		ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11	c.286-41_286-33delGCCCTCCCT		intron_variant		1	NM_207346.3	ENSP00000327487.6

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32126 AN: 151100 Hom.: 4663 Cov.: 27

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.0200

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.135 AC: 25338 AN: 188328 Hom.: 2123 AF XY: 0.131 AC XY: 13328 AN XY: 101962

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.0990

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0781

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.139 AC: 193280 AN: 1389602 Hom.: 14528 AF XY: 0.138 AC XY: 95189 AN XY: 688230

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0554

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.213 AC: 32177 AN: 151216 Hom.: 4677 Cov.: 27 AF XY: 0.209 AC XY: 15459 AN XY: 73946

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.197

Bravo AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

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: rs58038334; hg19: chr17-73513182;