rs7216673

Variant names:

• chr17-75516572-G-A
• rs7216673
• NM_207346.3:c.12G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-75516572-G-A
• chr17-75516572-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_207346.3(TSEN54):​c.12G>A​(p.Glu4Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000609 in 1,149,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: TSEN54 NM_207346.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.89
• Publications: 16 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-75516572-G-A is Benign according to our data. Variant chr17-75516572-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2882085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.89 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	NM_207346.3	MANE Select	c.12G>A	p.Glu4Glu	synonymous	Exon 1 of 11	NP_997229.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.12G>A	p.Glu4Glu	synonymous	Exon 1 of 11	ENSP00000327487.6
	TSEN54	ENST00000680999.1		c.12G>A	p.Glu4Glu	synonymous	Exon 1 of 11	ENSP00000504984.1
	TSEN54	ENST00000545228.3	TSL:5	c.12G>A	p.Glu4Glu	synonymous	Exon 1 of 11	ENSP00000438169.3

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149470 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000500 AC: 5 AN: 1000408 Hom.: 0 Cov.: 57 AF XY: 0.0000106 AC XY: 5 AN XY: 471028

African (AFR) AF: 0.000151 AC: 3 AN: 19894

American (AMR) AF: 0.00 AC: 0 AN: 5694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10878

East Asian (EAS) AF: 0.0000557 AC: 1 AN: 17962

South Asian (SAS) AF: 0.00 AC: 0 AN: 18852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2474

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 870166

Other (OTH) AF: 0.00 AC: 0 AN: 37782

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149470 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72880

African (AFR) AF: 0.0000244 AC: 1 AN: 41066

American (AMR) AF: 0.00 AC: 0 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67058

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.00 Hom.: 2148

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.91
DANN	Benign	0.93
PhyloP100		-2.9
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7216673; hg19: chr17-73512653;