3-9365210-T-G

Variant names:

• chr3-9365210-T-G
• rs376309040
• NM_001114092.2:c.142T>G

Variant summary

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

The NM_001114092.2(THUMPD3):​c.142T>G​(p.Phe48Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THUMPD3 NM_001114092.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21

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)

ACMG classification

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 rank	MANE	Protein	UniProt
THUMPD3	NM_001114092.2	c.142T>G	p.Phe48Val	missense_variant	Exon 2 of 10	ENST00000452837.7	NP_001107564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THUMPD3	ENST00000452837.7	c.142T>G	p.Phe48Val	missense_variant	Exon 2 of 10	1	NM_001114092.2	ENSP00000395893.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251484 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135914

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T;.;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;.;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.0	M;.;M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D;D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.89
MutPred		0.38		Loss of glycosylation at T43 (P = 0.0355);Loss of glycosylation at T43 (P = 0.0355);Loss of glycosylation at T43 (P = 0.0355);Loss of glycosylation at T43 (P = 0.0355);
MVP		0.85
MPC		0.37
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.65
gMVP		0.74

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

Other links and lift over

dbSNP: rs376309040; hg19: chr3-9406894;