rs78510537

Variant names:

• chr19-54191164-C-G
• rs78510537
• ENST00000302937.8:c.-4-197C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-54191164-C-G
• chr19-54191164-C-T

Variant summary

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

The NM_001282333.2(TSEN34):​c.-4-197C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,364,770 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (297 hom., cov: 33)
  • Exomes 𝑓: 0.013 (334 hom.)
• Consequence: TSEN34 NM_001282333.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.430
• Publications: 0 publications found

Genes affected

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

TSEN34 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2C

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.72).
• BP6: Variant 19-54191164-C-G is Benign according to our data. Variant chr19-54191164-C-G is described in ClinVar as Benign. ClinVar VariationId is 1246046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282333.2. 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
	TSEN34	NM_001282333.2		c.-4-197C>G		intron	N/A	NP_001269262.2	A0A590UJW4
	TSEN34	NM_001282332.2		c.-5+127C>G		intron	N/A	NP_001269261.1	Q9BSV6
	TSEN34	NM_001386740.1		c.-4-197C>G		intron	N/A	NP_001373669.1	Q9BSV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN34	ENST00000302937.8	TSL:1	c.-4-197C>G		intron	N/A	ENSP00000305524.4	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.-5+127C>G		intron	N/A	ENSP00000379667.1	Q9BSV6
	TSEN34	ENST00000667261.1		c.-4-197C>G		intron	N/A	ENSP00000499595.1	A0A590UJW4

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6861 AN: 151682 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00841

Gnomad OTH AF: 0.0366

GnomAD4 exome AF: 0.0128 AC: 15551 AN: 1212978 Hom.: 334 Cov.: 32 AF XY: 0.0127 AC XY: 7443 AN XY: 586782

African (AFR) AF: 0.115 AC: 2661 AN: 23204

American (AMR) AF: 0.0515 AC: 627 AN: 12176

Ashkenazi Jewish (ASJ) AF: 0.0137 AC: 225 AN: 16406

East Asian (EAS) AF: 0.0556 AC: 1596 AN: 28706

South Asian (SAS) AF: 0.0160 AC: 837 AN: 52324

European-Finnish (FIN) AF: 0.0438 AC: 1285 AN: 29344

Middle Eastern (MID) AF: 0.0165 AC: 55 AN: 3338

European-Non Finnish (NFE) AF: 0.00728 AC: 7263 AN: 997692

Other (OTH) AF: 0.0201 AC: 1002 AN: 49788

GnomAD4 genome AF: 0.0452 AC: 6866 AN: 151792 Hom.: 297 Cov.: 33 AF XY: 0.0457 AC XY: 3391 AN XY: 74192

African (AFR) AF: 0.113 AC: 4673 AN: 41400

American (AMR) AF: 0.0378 AC: 578 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3468

East Asian (EAS) AF: 0.0534 AC: 272 AN: 5098

South Asian (SAS) AF: 0.0144 AC: 69 AN: 4804

European-Finnish (FIN) AF: 0.0541 AC: 572 AN: 10582

Middle Eastern (MID) AF: 0.0139 AC: 4 AN: 288

European-Non Finnish (NFE) AF: 0.00842 AC: 571 AN: 67852

Other (OTH) AF: 0.0367 AC: 77 AN: 2098

Alfa AF: 0.00453 Hom.: 1

Bravo AF: 0.0504

Asia WGS AF: 0.0290 AC: 103 AN: 3476

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	-0.72
CADD	Benign	9.3
DANN	Benign	0.75
PhyloP100		-0.43
PromoterAI		-0.12	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: rs78510537; hg19: chr19-54695015;