rs373844254

Variant names:

• chr3-9366974-A-C
• rs373844254
• NM_001114092.2:c.319A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-9366974-A-C
• chr3-9366974-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114092.2(THUMPD3):​c.319A>C​(p.Lys107Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THUMPD3 NM_001114092.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.54

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36794764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THUMPD3	NM_001114092.2	c.319A>C	p.Lys107Gln	missense_variant	Exon 3 of 10	ENST00000452837.7	NP_001107564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THUMPD3	ENST00000452837.7	c.319A>C	p.Lys107Gln	missense_variant	Exon 3 of 10	1	NM_001114092.2	ENSP00000395893.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461136 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726878

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T;.;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;.;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.9	M;.;M;M
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.057	T;D;T;T
Sift4G	Benign	0.13	T;D;T;T
Polyphen		0.99	D;.;D;D
Vest4		0.53
MutPred		0.39		Loss of methylation at K107 (P = 0.004);Loss of methylation at K107 (P = 0.004);Loss of methylation at K107 (P = 0.004);Loss of methylation at K107 (P = 0.004);
MVP		0.80
MPC		0.22
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.49

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: rs373844254; hg19: chr3-9408658;