rs971572

Variant names:

• chr1-184099374-C-A
• rs971572
• ENST00000643916.1:n.*116-13491C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-184099374-C-A
• chr1-184099374-C-G
• chr1-184099374-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000644592.1(TSEN15):​n.354-20346C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,802 control chromosomes in the GnomAD database, including 7,911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7911 hom., cov: 31)
• Consequence: TSEN15 ENST00000644592.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.901
• Publications: 7 publications found

Genes affected

TSEN15 (HGNC:16791): (tRNA splicing endonuclease subunit 15) This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

TSEN15 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 2F

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• pontocerebellar hypoplasia type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286655 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644592.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSEN15	ENST00000643916.1		n.*116-13491C>A		intron	N/A	ENSP00000494533.1	A0A2R8Y5L0
	TSEN15	ENST00000644592.1		n.354-20346C>A		intron	N/A	ENSP00000495621.1	A0A2R8YG40
	ENSG00000286655	ENST00000664793.1		n.68-16489G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46410 AN: 151684 Hom.: 7911 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46426 AN: 151802 Hom.: 7911 Cov.: 31 AF XY: 0.310 AC XY: 22967 AN XY: 74180

African (AFR) AF: 0.159 AC: 6598 AN: 41382

American (AMR) AF: 0.304 AC: 4625 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3464

East Asian (EAS) AF: 0.579 AC: 2977 AN: 5144

South Asian (SAS) AF: 0.362 AC: 1738 AN: 4802

European-Finnish (FIN) AF: 0.403 AC: 4254 AN: 10548

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24410 AN: 67918

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.331 Hom.: 25700

Bravo AF: 0.293

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.8
DANN	Benign	0.76
PhyloP100		0.90

Splicing

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

Other links and lift over

dbSNP: rs971572; hg19: chr1-184068508; COSMIC: COSV59996059;