3-9371314-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114092.2(THUMPD3):ā€‹c.585G>Cā€‹(p.Glu195Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,992 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

THUMPD3
NM_001114092.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.199
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-AS1 (HGNC:44478): (THUMPD3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09045547).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THUMPD3NM_001114092.2 linkuse as main transcriptc.585G>C p.Glu195Asp missense_variant 4/10 ENST00000452837.7 NP_001107564.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THUMPD3ENST00000452837.7 linkuse as main transcriptc.585G>C p.Glu195Asp missense_variant 4/101 NM_001114092.2 ENSP00000395893 P1
THUMPD3-AS1ENST00000468186.5 linkuse as main transcriptn.2875+18976C>G intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250822
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135620
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461796
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJan 10, 2022The c.585G>C (p.E195D) alteration is located in exon 4 (coding exon 3) of the THUMPD3 gene. This alteration results from a G to C substitution at nucleotide position 585, causing the glutamic acid (E) at amino acid position 195 to be replaced by an aspartic acid (D). 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
0.096
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
12
DANN
Benign
0.97
DEOGEN2
Benign
0.0059
T;T;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.65
.;.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.090
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.0
M;M;M
MutationTaster
Benign
0.74
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.060
Sift
Uncertain
0.020
D;D;D
Sift4G
Benign
0.13
T;T;T
Polyphen
0.016
B;B;B
Vest4
0.21
MutPred
0.34
Loss of methylation at K194 (P = 0.0779);Loss of methylation at K194 (P = 0.0779);Loss of methylation at K194 (P = 0.0779);
MVP
0.48
MPC
0.049
ClinPred
0.048
T
GERP RS
-4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.29

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.

Other links and lift over

dbSNP: rs1329412069; hg19: chr3-9412998; API