3-9371339-G-C

Variant names:

• chr3-9371339-G-C
• rs200032940
• NM_001114092.2:c.610G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114092.2(THUMPD3):​c.610G>C​(p.Asp204His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D204Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THUMPD3 NM_001114092.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16635758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114092.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD3	NM_001114092.2	MANE Select	c.610G>C	p.Asp204His	missense	Exon 4 of 10	NP_001107564.1	Q9BV44
	THUMPD3	NM_015453.3		c.610G>C	p.Asp204His	missense	Exon 4 of 10	NP_056268.2	Q9BV44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD3	ENST00000452837.7	TSL:1 MANE Select	c.610G>C	p.Asp204His	missense	Exon 4 of 10	ENSP00000395893.2	Q9BV44
	THUMPD3	ENST00000515662.6	TSL:1	c.610G>C	p.Asp204His	missense	Exon 4 of 10	ENSP00000424064.1	Q9BV44
	THUMPD3-AS1	ENST00000468186.5	TSL:1	n.2875+18951C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.098
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.60
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.039	D
Sift4G	Uncertain	0.044	D
Polyphen		0.92	P
Vest4		0.14
MutPred		0.50		Gain of helix (P = 0.0496)
MVP		0.65
MPC		0.23
ClinPred		0.58	D
GERP RS		5.0
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.45
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs200032940; hg19: chr3-9413023;