rs953562498

Variant names:

• chr1-184051791-C-T
• rs953562498
• NM_052965.4:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_052965.4(TSEN15):​c.36C>T​(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,523,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: TSEN15 NM_052965.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663
• Publications: 0 publications found

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]

TSEN15 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 2F

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-184051791-C-T is Benign according to our data. Variant chr1-184051791-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1317347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.663 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052965.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	NM_052965.4	MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 5	NP_443197.1	Q8WW01-1
	TSEN15	NM_001300764.2		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 5	NP_001287693.1	A0A2U3TZM3
	TSEN15	NM_001363643.2		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 4	NP_001350572.1	A0A2R8YDU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	ENST00000645668.2	MANE Select	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 5	ENSP00000493902.2	Q8WW01-1
	TSEN15	ENST00000361641.6	TSL:1	c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 5	ENSP00000355299.2	A0A2U3TZM3
	TSEN15	ENST00000462677.3	TSL:1	n.36C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000432397.2	H0YCV5

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 5 AN: 124764 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000795 AC: 109 AN: 1370958 Hom.: 0 Cov.: 29 AF XY: 0.0000858 AC XY: 58 AN XY: 676058

African (AFR) AF: 0.00 AC: 0 AN: 29370

American (AMR) AF: 0.00 AC: 0 AN: 34194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24494

East Asian (EAS) AF: 0.00 AC: 0 AN: 33564

South Asian (SAS) AF: 0.00 AC: 0 AN: 76682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 0.0000993 AC: 106 AN: 1067904

Other (OTH) AF: 0.0000527 AC: 3 AN: 56944

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74346

African (AFR) AF: 0.0000965 AC: 4 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		-0.66
PromoterAI		0.065	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs953562498; hg19: chr1-184020925;