rs61738765

Variant names:

• chr1-184051687-G-A
• rs61738765
• ENST00000361641.6:c.-69G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000361641.6(TSEN15):​c.-69G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,305,020 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (32 hom.)
• Consequence: TSEN15 ENST00000361641.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.532
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-184051687-G-A is Benign according to our data. Variant chr1-184051687-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361641.6. 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.-69G>A		upstream_gene	N/A	NP_443197.1	Q8WW01-1
	TSEN15	NM_001300764.2		c.-69G>A		upstream_gene	N/A	NP_001287693.1	A0A2U3TZM3
	TSEN15	NM_001363643.2		c.-69G>A		upstream_gene	N/A	NP_001350572.1	A0A2R8YDU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	ENST00000361641.6	TSL:1	c.-69G>A		5_prime_UTR	Exon 1 of 5	ENSP00000355299.2	A0A2U3TZM3
	TSEN15	ENST00000643231.1		c.-69G>A		5_prime_UTR	Exon 1 of 4	ENSP00000494932.1	A0A2R8YDU8
	TSEN15	ENST00000423085.7	TSL:2	c.-69G>A		5_prime_UTR	Exon 1 of 4	ENSP00000402002.2	Q8WW01-2

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2371 AN: 152130 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00137 AC: 1576 AN: 1152778 Hom.: 32 Cov.: 29 AF XY: 0.00124 AC XY: 687 AN XY: 553586

African (AFR) AF: 0.0560 AC: 1290 AN: 23024

American (AMR) AF: 0.00462 AC: 41 AN: 8884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15436

East Asian (EAS) AF: 0.0000372 AC: 1 AN: 26912

South Asian (SAS) AF: 0.000177 AC: 7 AN: 39626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26904

Middle Eastern (MID) AF: 0.000952 AC: 3 AN: 3152

European-Non Finnish (NFE) AF: 0.0000520 AC: 50 AN: 962038

Other (OTH) AF: 0.00393 AC: 184 AN: 46802

GnomAD4 genome AF: 0.0156 AC: 2378 AN: 152242 Hom.: 59 Cov.: 32 AF XY: 0.0151 AC XY: 1123 AN XY: 74438

African (AFR) AF: 0.0543 AC: 2256 AN: 41564

American (AMR) AF: 0.00543 AC: 83 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68002

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00884 Hom.: 10

Bravo AF: 0.0177

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		0.53
PromoterAI		0.040	Neutral
Mutation Taster		=300/0	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: rs61738765; hg19: chr1-184020821;