rs72851941

Variant names:

• chr17-75516282-C-T
• rs72851941
• ENST00000434205.8:c.-187C>T

Variant summary

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

The ENST00000679370.1(TSEN54):​n.339C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 180,924 control chromosomes in the GnomAD database, including 3,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3361 hom., cov: 33)
  • Exomes 𝑓: 0.12 (235 hom.)
• Consequence: TSEN54 ENST00000679370.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-75516282-C-T is Benign according to our data. Variant chr17-75516282-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679370.1. 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.-279C>T		upstream_gene	N/A	NP_997229.2	Q7Z6J9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN54	ENST00000434205.8	TSL:5	c.-187C>T		5_prime_UTR	Exon 1 of 10	ENSP00000406559.4	E7EN92
	TSEN54	ENST00000679370.1		n.339C>T		non_coding_transcript_exon	Exon 1 of 9
	TSEN54	ENST00000333213.11	TSL:1 MANE Select	c.-279C>T		upstream_gene	N/A	ENSP00000327487.6	Q7Z6J9-1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28067 AN: 152016 Hom.: 3351 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.122 AC: 3501 AN: 28790 Hom.: 235 Cov.: 3 AF XY: 0.120 AC XY: 1876 AN XY: 15626

African (AFR) AF: 0.299 AC: 177 AN: 592

American (AMR) AF: 0.0901 AC: 69 AN: 766

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 113 AN: 770

East Asian (EAS) AF: 0.0149 AC: 17 AN: 1142

South Asian (SAS) AF: 0.116 AC: 34 AN: 294

European-Finnish (FIN) AF: 0.0915 AC: 274 AN: 2996

Middle Eastern (MID) AF: 0.160 AC: 24 AN: 150

European-Non Finnish (NFE) AF: 0.128 AC: 2601 AN: 20358

Other (OTH) AF: 0.111 AC: 192 AN: 1722

GnomAD4 genome AF: 0.185 AC: 28114 AN: 152134 Hom.: 3361 Cov.: 33 AF XY: 0.181 AC XY: 13472 AN XY: 74408

African (AFR) AF: 0.336 AC: 13922 AN: 41464

American (AMR) AF: 0.133 AC: 2037 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5174

South Asian (SAS) AF: 0.102 AC: 491 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1151 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9391 AN: 67980

Other (OTH) AF: 0.179 AC: 378 AN: 2116

Alfa AF: 0.175 Hom.: 380

Bravo AF: 0.192

Asia WGS AF: 0.0890 AC: 313 AN: 3478

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	-0.81
CADD	Benign	2.3
DANN	Benign	0.79
PhyloP100		-1.0
PromoterAI		0.0015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72851941; hg19: chr17-73512363;