Variant 3-9371165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000452837.7(THUMPD3):c.436C>T(p.Arg146Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,611,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

THUMPD3
ENST00000452837.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

THUMPD3 (HGNC:24493): (THUMP domain containing 3) Predicted to enable tRNA (guanine) methyltransferase activity. Predicted to be involved in tRNA methylation. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

THUMPD3 links:

THUMPD3-AS1 (HGNC:):

THUMPD3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066109866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THUMPD3	NM_001114092.2 linkuse as main transcript	c.436C>T	p.Arg146Cys	missense_variant	4/10	ENST00000452837.7	NP_001107564.1	Q9BV44A0A024R2D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THUMPD3	ENST00000452837.7 linkuse as main transcript	c.436C>T	p.Arg146Cys	missense_variant	4/10	1	NM_001114092.2	ENSP00000395893.2		Q9BV44

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000402

AC:

AN:

248556

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134470

show subpopulations

Gnomad AFR exome

AF:

0.000443

Gnomad AMR exome

AF:

0.0000293

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1459364

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

725724

show subpopulations

Gnomad4 AFR exome

AF:

0.000270

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000921

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000265

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:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

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

Oct 12, 2021

The c.436C>T (p.R146C) alteration is located in exon 4 (coding exon 3) of the THUMPD3 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the arginine (R) at amino acid position 146 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;T;T

Eigen

Benign

-0.069

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.063

Sift

Benign

0.057

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.10

B;B;B

Vest4

0.19

MVP

0.59

MPC

0.068

ClinPred

0.10

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.41

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