2-39744386-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025264.5(THUMPD2):​c.1171C>A​(p.Leu391Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,417,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

THUMPD2
NM_025264.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50
Variant links:
Genes affected
THUMPD2 (HGNC:14890): (THUMP domain containing 2) Predicted to enable tRNA (guanine) methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THUMPD2NM_025264.5 linkc.1171C>A p.Leu391Ile missense_variant 9/10 ENST00000505747.6 NP_079540.2 Q9BTF0-1Q969Z2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THUMPD2ENST00000505747.6 linkc.1171C>A p.Leu391Ile missense_variant 9/101 NM_025264.5 ENSP00000423933.1 Q9BTF0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000212
AC:
3
AN:
1417156
Hom.:
0
Cov.:
27
AF XY:
0.00000142
AC XY:
1
AN XY:
705002
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:
0.0000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 30, 2024The c.1171C>A (p.L391I) alteration is located in exon 9 (coding exon 9) of the THUMPD2 gene. This alteration results from a C to A substitution at nucleotide position 1171, causing the leucine (L) at amino acid position 391 to be replaced by an isoleucine (I). 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
0.088
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.062
T
Eigen
Benign
0.072
Eigen_PC
Benign
0.038
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0082
T
MetaRNN
Uncertain
0.52
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.23
Sift
Benign
0.12
T
Sift4G
Uncertain
0.019
D
Polyphen
0.98
D
Vest4
0.36
MutPred
0.74
Gain of methylation at K388 (P = 0.0933);
MVP
0.33
MPC
0.015
ClinPred
0.85
D
GERP RS
1.7
Varity_R
0.070
gMVP
0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-39971526; API