2-39755399-T-A

Variant names:

• chr2-39755399-T-A
• rs550205144
• NM_025264.5:c.974A>T

Variant summary

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

The NM_025264.5(THUMPD2):​c.974A>T​(p.Tyr325Phe) 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. 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. Y325C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THUMPD2 NM_025264.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 0 publications found

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]

LOC124905994 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025264.5. 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
	THUMPD2	NM_025264.5	MANE Select	c.974A>T	p.Tyr325Phe	missense	Exon 8 of 10	NP_079540.2	Q9BTF0-1
	THUMPD2	NM_001321468.1		c.974A>T	p.Tyr325Phe	missense	Exon 8 of 11	NP_001308397.1
	THUMPD2	NM_001321469.1		c.695A>T	p.Tyr232Phe	missense	Exon 8 of 10	NP_001308398.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD2	ENST00000505747.6	TSL:1 MANE Select	c.974A>T	p.Tyr325Phe	missense	Exon 8 of 10	ENSP00000423933.1	Q9BTF0-1
	THUMPD2	ENST00000378727.8	TSL:1	n.*183A>T		non_coding_transcript_exon	Exon 9 of 11	ENSP00000368001.4	Q9BTF0-2
	THUMPD2	ENST00000460072.5	TSL:1	n.1935A>T		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	27
DANN	Benign	0.89
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.50	N
PhyloP100		3.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.48	T
Sift4G	Benign	0.44	T
Polyphen		0.46	P
Vest4		0.44
MutPred		0.47		Loss of phosphorylation at Y325 (P = 0.0407)
MVP		0.24
MPC		0.063
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.66
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs550205144; hg19: chr2-39982539;