9-128309687-T-C

Position:

chr9-128309687-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015679.3(TRUB2):c.859A>G(p.Thr287Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TRUB2
NM_015679.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.626

Variant links:

Genes affected

TRUB2 (HGNC:17170): (TruB pseudouridine synthase family member 2) Pseudouridine is an abundant component of rRNAs and tRNAs and is enzymatically generated by isomerization of uridine by pseudouridine synthase (Zucchini et al., 2003 [PubMed 12736709]).[supplied by OMIM, Mar 2008]

TRUB2 links:

SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SWI5 links:

TRUB2 (HGNC:):

TRUB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019541055).

BP6

Variant 9-128309687-T-C is Benign according to our data. Variant chr9-128309687-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3183551.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRUB2	NM_015679.3 linkuse as main transcript	c.859A>G	p.Thr287Ala	missense_variant	8/8	ENST00000372890.6	NP_056494.1	O95900-1A0A024R886
TRUB2	NM_001329861.2 linkuse as main transcript	c.727A>G	p.Thr243Ala	missense_variant	7/7		NP_001316790.1	O95900
TRUB2	NM_001329862.2 linkuse as main transcript	c.691A>G	p.Thr231Ala	missense_variant	8/8		NP_001316791.1	O95900-2
TRUB2	NM_001329863.2 linkuse as main transcript	c.547A>G	p.Thr183Ala	missense_variant	9/9		NP_001316792.1	O95900

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRUB2	ENST00000372890.6 linkuse as main transcript	c.859A>G	p.Thr287Ala	missense_variant	8/8	1	NM_015679.3	ENSP00000361982.4	O95900-1
SWI5	ENST00000652598.1 linkuse as main transcript	n.329-4143T>C		intron_variant				ENSP00000498805.2	A0A494C0Z4
TRUB2	ENST00000460320.1 linkuse as main transcript	n.*6A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251350

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.3

DANN

Benign

0.18

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.11

M_CAP

Benign

0.0046

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.0

PrimateAI

Benign

0.38

PROVEAN

Benign

0.35

REVEL

Benign

0.055

Sift

Benign

0.87

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.028

MVP

0.067

MPC

0.18

ClinPred

0.010

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.19

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

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