rs6501820

Variant names:

• chr17-75522203-G-C
• rs6501820
• NM_207346.3:c.1122G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-75522203-G-C
• chr17-75522203-G-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_207346.3(TSEN54):​c.1122G>C​(p.Arg374Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,549,836 control chromosomes in the GnomAD database, including 616,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60900 hom., cov: 33)
  • Exomes 𝑓: 0.89 (555413 hom.)
• Consequence: TSEN54 NM_207346.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: 0.0780
• Publications: 19 publications found

Genes affected

TSEN54 (HGNC:27561): (tRNA splicing endonuclease subunit 54) This gene encodes a subunit of the tRNA splicing endonuclease complex, which catalyzes the removal of introns from precursor tRNAs. The complex is also implicated in pre-mRNA 3-prime end processing. Mutations in this gene result in pontocerebellar hypoplasia type 2.[provided by RefSeq, Oct 2009]

TSEN54 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 2A

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• pontocerebellar hypoplasia type 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• pontocerebellar hypoplasia type 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• 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=-0.62).
• BP6: Variant 17-75522203-G-C is Benign according to our data. Variant chr17-75522203-G-C is described in ClinVar as Benign. ClinVar VariationId is 96670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.078 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207346.3. 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
	TSEN54	NM_207346.3	MANE Select	c.1122G>C	p.Arg374Arg	synonymous	Exon 8 of 11	NP_997229.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.1122G>C	p.Arg374Arg	synonymous	Exon 8 of 11	ENSP00000327487.6
	TSEN54	ENST00000680999.1		c.1122G>C	p.Arg374Arg	synonymous	Exon 8 of 11	ENSP00000504984.1
	TSEN54	ENST00000915433.1		c.1122G>C	p.Arg374Arg	synonymous	Exon 8 of 11	ENSP00000585492.1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135078 AN: 152078 Hom.: 60847 Cov.: 33

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.878

GnomAD2 exomes AF: 0.814 AC: 127526 AN: 156712 AF XY: 0.829

Gnomad AFR exome AF: 0.982

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.526

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.908

Gnomad OTH exome AF: 0.844

GnomAD4 exome AF: 0.887 AC: 1239748 AN: 1397640 Hom.: 555413 Cov.: 81 AF XY: 0.888 AC XY: 611569 AN XY: 688622

African (AFR) AF: 0.982 AC: 31006 AN: 31584

American (AMR) AF: 0.563 AC: 20513 AN: 36414

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 20664 AN: 25112

East Asian (EAS) AF: 0.513 AC: 18347 AN: 35746

South Asian (SAS) AF: 0.891 AC: 70610 AN: 79274

European-Finnish (FIN) AF: 0.887 AC: 42696 AN: 48156

Middle Eastern (MID) AF: 0.927 AC: 5215 AN: 5628

European-Non Finnish (NFE) AF: 0.910 AC: 980350 AN: 1077822

Other (OTH) AF: 0.869 AC: 50347 AN: 57904

GnomAD4 genome AF: 0.888 AC: 135185 AN: 152196 Hom.: 60900 Cov.: 33 AF XY: 0.882 AC XY: 65653 AN XY: 74406

African (AFR) AF: 0.975 AC: 40532 AN: 41556

American (AMR) AF: 0.703 AC: 10743 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3472

East Asian (EAS) AF: 0.550 AC: 2833 AN: 5152

South Asian (SAS) AF: 0.876 AC: 4225 AN: 4824

European-Finnish (FIN) AF: 0.885 AC: 9382 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61605 AN: 67996

Other (OTH) AF: 0.877 AC: 1851 AN: 2110

Alfa AF: 0.896 Hom.: 19813

Bravo AF: 0.872

Asia WGS AF: 0.762 AC: 2650 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	4	not provided (4)
-	-	1	Pontocerebellar hypoplasia type 2A (1)
-	-	1	Pontocerebellar hypoplasia type 4 (1)
-	-	1	Pontocerebellar hypoplasia type 5 (1)
-	-	1	Pontoneocerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		0.078
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6501820; hg19: chr17-73518284; COSMIC: COSV51344477; COSMIC: COSV51344477;