rs11879943

Variant names:

• chr19-54192316-C-A
• rs11879943
• NM_001077446.4:c.688C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54192316-C-A
• chr19-54192316-C-G
• chr19-54192316-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001077446.4(TSEN34):​c.688C>A​(p.Arg230Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,614,070 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (116 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (618 hom.)
• Consequence: TSEN34 NM_001077446.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.554
• Publications: 10 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-54192316-C-A is Benign according to our data. Variant chr19-54192316-C-A is described in ClinVar as Benign. ClinVar VariationId is 137754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.554 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

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.688C>A	p.Arg230Arg	synonymous	Exon 3 of 4	NP_001070914.1	Q9BSV6
	TSEN34	NM_001282333.2		c.688C>A	p.Arg230Arg	synonymous	Exon 4 of 6	NP_001269262.2	A0A590UJW4
	TSEN34	NM_001282332.2		c.688C>A	p.Arg230Arg	synonymous	Exon 4 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.688C>A	p.Arg230Arg	synonymous	Exon 3 of 4	ENSP00000379671.2	Q9BSV6
	TSEN34	ENST00000302937.8	TSL:1	c.688C>A	p.Arg230Arg	synonymous	Exon 4 of 5	ENSP00000305524.4	Q9BSV6
	TSEN34	ENST00000396383.5	TSL:1	c.688C>A	p.Arg230Arg	synonymous	Exon 4 of 5	ENSP00000379667.1	Q9BSV6

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3617 AN: 152106 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0211 AC: 5246 AN: 249046 AF XY: 0.0178

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.0300

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.0310

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00856 AC: 12510 AN: 1461846 Hom.: 618 Cov.: 35 AF XY: 0.00811 AC XY: 5898 AN XY: 727220

African (AFR) AF: 0.0519 AC: 1738 AN: 33476

American (AMR) AF: 0.0287 AC: 1284 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00268 AC: 70 AN: 26136

East Asian (EAS) AF: 0.151 AC: 5995 AN: 39700

South Asian (SAS) AF: 0.00347 AC: 299 AN: 86256

European-Finnish (FIN) AF: 0.0293 AC: 1565 AN: 53420

Middle Eastern (MID) AF: 0.00314 AC: 18 AN: 5736

European-Non Finnish (NFE) AF: 0.000622 AC: 692 AN: 1112008

Other (OTH) AF: 0.0141 AC: 849 AN: 60390

GnomAD4 genome AF: 0.0238 AC: 3630 AN: 152224 Hom.: 116 Cov.: 32 AF XY: 0.0250 AC XY: 1864 AN XY: 74428

African (AFR) AF: 0.0509 AC: 2114 AN: 41526

American (AMR) AF: 0.0184 AC: 281 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.131 AC: 679 AN: 5166

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4830

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68016

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0116 Hom.: 76

Bravo AF: 0.0258

Asia WGS AF: 0.0700 AC: 243 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.7
DANN	Benign	0.81
PhyloP100		0.55
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: rs11879943; hg19: chr19-54696167; COSMIC: COSV55475896; COSMIC: COSV55475896;