rs1438493791

Positions:

• chr17-75516870-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207346.3(TSEN54):​c.181G>A​(p.Glu61Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TSEN54 NM_207346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.34

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSEN54	NM_207346.3	c.181G>A	p.Glu61Lys	missense_variant	2/11	ENST00000333213.11	NP_997229.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSEN54	ENST00000333213.11	c.181G>A	p.Glu61Lys	missense_variant	2/11	1	NM_207346.3	ENSP00000327487	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000593 AC: 1 AN: 168572 Hom.: 0 AF XY: 0.0000107 AC XY: 1 AN XY: 93832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412162 Hom.: 0 Cov.: 51 AF XY: 0.00000143 AC XY: 1 AN XY: 699388

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000249

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Mar 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.29
Sift	Benign	0.031	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.35		Gain of MoRF binding (P = 0.0061);
MVP		0.66
MPC		0.58
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.65
gMVP		0.64

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: rs1438493791; hg19: chr17-73512951;