chr3-9371348-T-C

Variant names:

• chr3-9371348-T-C
• rs2032021866
• NM_001114092.2:c.619T>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.619T>C​(p.Ser207Pro) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: THUMPD3 NM_001114092.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.622
• 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=0.191984).

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.619T>C	p.Ser207Pro	missense	Exon 4 of 10	NP_001107564.1	Q9BV44
	THUMPD3	NM_015453.3		c.619T>C	p.Ser207Pro	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.619T>C	p.Ser207Pro	missense	Exon 4 of 10	ENSP00000395893.2	Q9BV44
	THUMPD3	ENST00000515662.6	TSL:1	c.619T>C	p.Ser207Pro	missense	Exon 4 of 10	ENSP00000424064.1	Q9BV44
	THUMPD3-AS1	ENST00000468186.5	TSL:1	n.2875+18942A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.62
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Polyphen		0.95	P
Vest4		0.20
MutPred		0.42		Gain of catalytic residue at S207 (P = 0.002)
MVP		0.72
MPC		0.34
ClinPred		0.69	D
GERP RS		5.9
PromoterAI		0.0054	Neutral
Varity_R		0.17
gMVP		0.53
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs2032021866; hg19: chr3-9413032; COSMIC: COSV100560707; COSMIC: COSV100560707;