chr1-184051831-G-C

Variant names:

• chr1-184051831-G-C
• rs1020949674
• NM_052965.4:c.76G>C

Variant summary

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

The NM_052965.4(TSEN15):​c.76G>C​(p.Asp26His) 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. 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. D26Y) 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: 0.599

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=0.20487249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSEN15	NM_052965.4	c.76G>C	p.Asp26His	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.76G>C	p.Asp26His	missense_variant	Exon 1 of 5		NM_052965.4	ENSP00000493902.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.0060	T;.;.;.;.;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.76	T;T;T;T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.68	.;N;N;.;N;.;.
REVEL	Benign	0.13
Sift	Benign	0.087	.;T;T;.;T;.;.
Sift4G	Benign	0.20	.;T;T;.;T;.;.
Polyphen		0.0	B;.;.;.;.;.;.
Vest4		0.13, 0.11, 0.13
MutPred		0.71		Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);
MVP		0.34
MPC		0.94
ClinPred		0.12	T
GERP RS		-1.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.066
gMVP		0.27

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: rs1020949674; hg19: chr1-184020965;