rs184898622

Variant names:

• chr19-54191403-G-A
• rs184898622
• NM_001077446.4:c.39G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54191403-G-A
• chr19-54191403-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001077446.4(TSEN34):​c.39G>A​(p.Val13Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,549,440 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: TSEN34 NM_001077446.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.05
• 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: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 19-54191403-G-A is Benign according to our data. Variant chr19-54191403-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077446.4. 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
	TSEN34	NM_001077446.4	MANE Select	c.39G>A	p.Val13Val	synonymous	Exon 1 of 4	NP_001070914.1	Q9BSV6
	TSEN34	NM_001282333.2		c.39G>A	p.Val13Val	synonymous	Exon 2 of 6	NP_001269262.2	A0A590UJW4
	TSEN34	NM_001282332.2		c.39G>A	p.Val13Val	synonymous	Exon 2 of 5	NP_001269261.1	Q9BSV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN34	ENST00000396388.3	TSL:1 MANE Select	c.39G>A	p.Val13Val	synonymous	Exon 1 of 4	ENSP00000379671.2	Q9BSV6
	TSEN34	ENST00000302937.8	TSL:1	c.39G>A	p.Val13Val	synonymous	Exon 2 of 5	ENSP00000305524.4	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.39G>A	p.Val13Val	synonymous	Exon 2 of 5	ENSP00000379667.1	Q9BSV6

Frequencies

GnomAD3 genomes AF: 0.00387 AC: 589 AN: 152198 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00100 AC: 147 AN: 146602 AF XY: 0.000812

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.000360

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000262

Gnomad OTH exome AF: 0.000472

GnomAD4 exome AF: 0.000465 AC: 650 AN: 1397130 Hom.: 1 Cov.: 35 AF XY: 0.000422 AC XY: 291 AN XY: 689292

African (AFR) AF: 0.0118 AC: 372 AN: 31524

American (AMR) AF: 0.00134 AC: 48 AN: 35738

Ashkenazi Jewish (ASJ) AF: 0.000636 AC: 16 AN: 25154

East Asian (EAS) AF: 0.00 AC: 0 AN: 35774

South Asian (SAS) AF: 0.00 AC: 0 AN: 79338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48774

Middle Eastern (MID) AF: 0.00319 AC: 13 AN: 4080

European-Non Finnish (NFE) AF: 0.000121 AC: 131 AN: 1078950

Other (OTH) AF: 0.00121 AC: 70 AN: 57798

GnomAD4 genome AF: 0.00386 AC: 588 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00385 AC XY: 287 AN XY: 74468

African (AFR) AF: 0.0129 AC: 535 AN: 41576

American (AMR) AF: 0.00196 AC: 30 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00170 Hom.: 1

Bravo AF: 0.00488

Asia WGS AF: 0.000579 AC: 2 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.2
DANN	Benign	0.96
PhyloP100		1.1
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs184898622; hg19: chr19-54695254;