Variant chr16-1350144-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001001410.3(TSR3):c.617C>T(p.Ala206Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000247 in 1,460,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TSR3
NM_001001410.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

Variant links:

Genes affected

TSR3 (HGNC:14175): (TSR3 ribosome maturation factor) Enables transferase activity. Involved in enzyme-directed rRNA pseudouridine synthesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TSR3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSR3	NM_001001410.3 linkuse as main transcript	c.617C>T	p.Ala206Val	missense_variant	4/6	ENST00000007390.3	NP_001001410.1	Q9UJK0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSR3	ENST00000007390.3 linkuse as main transcript	c.617C>T	p.Ala206Val	missense_variant	4/6	1	NM_001001410.3	ENSP00000007390.2	Q9UJK0
TSR3	ENST00000566296.1 linkuse as main transcript	n.*51C>T		non_coding_transcript_exon_variant	3/4	3		ENSP00000455722.1	H3BQD4
TSR3	ENST00000566296.1 linkuse as main transcript	n.*51C>T		3_prime_UTR_variant	3/4	3		ENSP00000455722.1	H3BQD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249020

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1460030

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000825

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.617C>T (p.A206V) alteration is located in exon 4 (coding exon 4) of the TSR3 gene. This alteration results from a C to T substitution at nucleotide position 617, causing the alanine (A) at amino acid position 206 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.56

Sift

Benign

0.069

Sift4G

Uncertain

0.051

Polyphen

1.0

Vest4

0.67

MutPred

0.52

Loss of disorder (P = 0.1002);

MVP

0.21

MPC

0.28

ClinPred

0.91

GERP RS

5.0

Varity_R

0.33

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over