rs191600766

chr17-75521674-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207346.3(TSEN54):c.624-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000882 in 1,609,530 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (4 hom.)
• Consequence: TSEN54 NM_207346.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.255

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-75521674-A-G is Benign according to our data. Variant chr17-75521674-A-G is described in ClinVar as [Benign]. Clinvar id is 263296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000887 (135/152262) while in subpopulation AMR AF= 0.00274 (42/15302). AF 95% confidence interval is 0.00209. There are 1 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSEN54	NM_207346.3	c.624-31A>G		intron_variant		ENST00000333213.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSEN54	ENST00000333213.11	c.624-31A>G		intron_variant		1	NM_207346.3	P1

Frequencies

GnomAD3 genomes AF: 0.000887 AC: 135 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00116 AC: 288 AN: 248736 Hom.: 3 AF XY: 0.00134 AC XY: 181 AN XY: 134778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00319

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00147

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.000882 AC: 1285 AN: 1457268 Hom.: 4 Cov.: 29 AF XY: 0.000946 AC XY: 686 AN XY: 725238

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00311

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.0000759

Gnomad4 NFE exome AF: 0.000594

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.000887 AC: 135 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74450

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00201 Hom.: 1

Bravo AF: 0.00131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	12
Dann	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs191600766; hg19: chr17-73517755;