Variant 3-9366953-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001114092.2(THUMPD3):c.298G>C(p.Glu100Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00125 in 1,613,322 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

THUMPD3
NM_001114092.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

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:44478): (THUMPD3 antisense RNA 1)

THUMPD3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.104986906).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THUMPD3	NM_001114092.2 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 3 of 10	ENST00000452837.7	NP_001107564.1	Q9BV44A0A024R2D3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THUMPD3	ENST00000452837.7 link	c.298G>C	p.Glu100Gln	missense_variant	Exon 3 of 10	1	NM_001114092.2	ENSP00000395893.2		Q9BV44

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00109

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000446

AC:

112

AN:

250916

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.000942

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.00132

AC:

1930

AN:

1461256

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

913

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00160

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.000572

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000552

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000445

AC:

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

Dec 04, 2024

The c.298G>C (p.E100Q) alteration is located in exon 3 (coding exon 2) of the THUMPD3 gene. This alteration results from a G to C substitution at nucleotide position 298, causing the glutamic acid (E) at amino acid position 100 to be replaced by a glutamine (Q). 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

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0056

T;.;T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

.;T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

M;.;M;M

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.023

D;D;D;D

Sift4G

Uncertain

0.034

D;D;D;D

Polyphen

0.98

D;.;D;D

Vest4

0.40

MVP

0.78

MPC

0.068

ClinPred

0.12

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.61

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