1-184051777-G-A

Variant names:

• chr1-184051777-G-A
• rs1445474819
• NM_052965.4:c.22G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052965.4(TSEN15):​c.22G>A​(p.Glu8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000463 in 1,510,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E8Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: TSEN15 NM_052965.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057854146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN15	NM_052965.4	c.22G>A	p.Glu8Lys	missense_variant	Exon 1 of 5	ENST00000645668.2	NP_443197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSEN15	ENST00000645668.2	c.22G>A	p.Glu8Lys	missense_variant	Exon 1 of 5		NM_052965.4	ENSP00000493902.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000368 AC: 5 AN: 1358670 Hom.: 0 Cov.: 29 AF XY: 0.00000149 AC XY: 1 AN XY: 669574

Gnomad4 AFR exome AF: 0.0000346

Gnomad4 AMR exome AF: 0.00

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: 0.00000377

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74292

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0073	T;.;.;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.75	T;T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.058	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;.;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.81	.;N;N;.;N;.;.
REVEL	Benign	0.053
Sift	Benign	0.12	.;T;T;.;T;.;.
Sift4G	Benign	0.40	.;T;T;.;T;.;.
Polyphen		0.0010	B;.;.;.;.;.;.
Vest4		0.14, 0.17, 0.15
MutPred		0.21		Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);Gain of ubiquitination at E8 (P = 7e-04);
MVP		0.21
MPC		0.55
ClinPred		0.022	T
GERP RS		-1.9
Varity_R		0.063
gMVP		0.15

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: rs1445474819; hg19: chr1-184020911;