rs709160

Variant names:

• chr3-12484903-G-C
• rs709160
• NM_025265.4:c.-18+23G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-12484903-G-C
• chr3-12484903-G-T

Variant summary

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

The NM_025265.4(TSEN2):​c.-18+23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,124 control chromosomes in the GnomAD database, including 24,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24461 hom., cov: 32)
  • Exomes 𝑓: 0.37 (3 hom.)
• Consequence: TSEN2 NM_025265.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.11
• Publications: 8 publications found

Genes affected

TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

TSEN2 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2B

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.93).
• BP6: Variant 3-12484903-G-C is Benign according to our data. Variant chr3-12484903-G-C is described in ClinVar as Benign. ClinVar VariationId is 1273097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025265.4. 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
	TSEN2	NM_025265.4	MANE Select	c.-18+23G>C		intron	N/A	NP_079541.1	Q8NCE0-1
	TSEN2	NM_001321278.2		c.-18+386G>C		intron	N/A	NP_001308207.1	C9J7Z4
	TSEN2	NM_001145392.2		c.-18+275G>C		intron	N/A	NP_001138864.1	Q8NCE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN2	ENST00000284995.11	TSL:1 MANE Select	c.-18+23G>C		intron	N/A	ENSP00000284995.6	Q8NCE0-1
	TSEN2	ENST00000402228.7	TSL:1	c.-18+275G>C		intron	N/A	ENSP00000385976.3	Q8NCE0-1
	TSEN2	ENST00000454502.6	TSL:1	c.-18+386G>C		intron	N/A	ENSP00000392029.2	Q8NCE0-4

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82938 AN: 151968 Hom.: 24432 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.538

GnomAD4 exome AF: 0.368 AC: 14 AN: 38 Hom.: 3 Cov.: 0 AF XY: 0.300 AC XY: 9 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.643 AC: 9 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 5 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.546 AC: 83009 AN: 152086 Hom.: 24461 Cov.: 32 AF XY: 0.538 AC XY: 40016 AN XY: 74312

African (AFR) AF: 0.762 AC: 31615 AN: 41494

American (AMR) AF: 0.453 AC: 6925 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3470

East Asian (EAS) AF: 0.130 AC: 673 AN: 5166

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4818

European-Finnish (FIN) AF: 0.495 AC: 5232 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33764 AN: 67980

Other (OTH) AF: 0.537 AC: 1133 AN: 2110

Alfa AF: 0.515 Hom.: 2508

Bravo AF: 0.552

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

ClinVar submissions

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	-0.93
CADD	Benign	0.66
DANN	Benign	0.51
PhyloP100		-2.1
PromoterAI		-0.037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs709160; hg19: chr3-12526402;