Genetic Variant THUMPD2:p.Gly384Arg (chr2-39744407-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001321468.1(THUMPD2):c.1248G>C(p.Ter416Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,430,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

THUMPD2
NM_001321468.1 stop_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Publications

0 publications found

Variant links:

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]

THUMPD2 links:

LOC124905994 (HGNC:):

LOC124905994 links:

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ACMG classification

Classification was made for transcript

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

PM4

Stoplost variant in NM_001321468.1 Downstream stopcodon found after 427 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321468.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THUMPD2	NM_025264.5	MANE Select	c.1150G>C	p.Gly384Arg	missense	Exon 9 of 10	NP_079540.2	Q9BTF0-1
THUMPD2	NM_001321468.1		c.1248G>C	p.Ter416Tyrext*?	stop_lost	Exon 10 of 11	NP_001308397.1
THUMPD2	NM_001321474.1		c.1035G>C	p.Ter345Tyrext*?	stop_lost	Exon 8 of 9	NP_001308403.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THUMPD2	ENST00000505747.6	TSL:1 MANE Select	c.1150G>C	p.Gly384Arg	missense	Exon 9 of 10	ENSP00000423933.1	Q9BTF0-1
THUMPD2	ENST00000378727.8	TSL:1	n.*359G>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000368001.4	Q9BTF0-2
THUMPD2	ENST00000460072.5	TSL:1	n.2111G>C		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000536

AC:

AN:

223698

AF XY:

0.0000658

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1430678

Hom.:

Cov.:

AF XY:

0.0000520

AC XY:

AN XY:

711380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31442

American (AMR)

AF:

0.00

AC:

AN:

38246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

37480

South Asian (SAS)

AF:

0.000451

AC:

AN:

79778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1100402

Other (OTH)

AF:

0.0000169

AC:

AN:

59074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000742

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3466

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.013

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

M_CAP

Benign

0.0066

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

PhyloP100

2.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

REVEL

Benign

0.045

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.012

Vest4

0.25

MutPred

0.55

Gain of MoRF binding (P = 0.0162)

MVP

0.30

MPC

0.016

ClinPred

0.38

GERP RS

3.8

Varity_R

0.043

gMVP

0.46

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over