rs759083409

Variant names:

• chr1-184051795-A-C
• rs759083409
• NM_052965.4:c.40A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-184051795-A-C
• chr1-184051795-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052965.4(TSEN15):​c.40A>C​(p.Ser14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. S14G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSEN15 NM_052965.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14393854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN15	NM_052965.4	c.40A>C	p.Ser14Arg	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.40A>C	p.Ser14Arg	missense_variant	Exon 1 of 5		NM_052965.4	ENSP00000493902.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0071	T;.;.;.;.;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.81	T;T;T;T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	.;N;N;.;N;.;.
REVEL	Benign	0.057
Sift	Uncertain	0.011	.;D;D;.;D;.;.
Sift4G	Uncertain	0.029	.;D;D;.;D;.;.
Polyphen		0.77	P;.;.;.;.;.;.
Vest4		0.28, 0.35, 0.28
MutPred		0.18		Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);Loss of glycosylation at S14 (P = 0.0079);
MVP		0.29
MPC		0.83
ClinPred		0.69	D
GERP RS		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.22
gMVP		0.30

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: rs759083409; hg19: chr1-184020929;