dbSNP rs868148836: DTD1:p.Thr38Lys (chr20-18593800-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_080820.6(DTD1):c.113C>A(p.Thr38Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T38M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DTD1
NM_080820.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.48

Variant links:

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

DTD1 links:

ENSG00000284776 (HGNC:):

ENSG00000284776 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6 link	c.113C>A	p.Thr38Lys	missense_variant	Exon 2 of 6	ENST00000377452.4	NP_543010.3	Q8TEA8
DTD1	NM_001318043.2 link	c.113C>A	p.Thr38Lys	missense_variant	Exon 2 of 5		NP_001304972.1	Q8TEA8A0A2R8Y6X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTD1	ENST00000377452.4 link	c.113C>A	p.Thr38Lys	missense_variant	Exon 2 of 6	1	NM_080820.6	ENSP00000366672.4	Q8TEA8
ENSG00000284776	ENST00000618693.4 link	c.188C>A	p.Thr63Lys	missense_variant	Exon 2 of 5	5		ENSP00000482916.1	A0A087WZV9
DTD1	ENST00000494921.2 link	c.113C>A	p.Thr38Lys	missense_variant	Exon 2 of 5	2		ENSP00000495845.1	A0A2R8Y6X2
DTD1	ENST00000647441.1 link	n.113C>A		non_coding_transcript_exon_variant	Exon 2 of 7			ENSP00000493969.1	A0A2R8YCT7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461338

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726980

show subpopulations

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.8

.;M;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.6

.;D;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.022

.;D;.

Sift4G

Benign

0.072

T;D;.

Polyphen

0.21

.;B;.

Vest4

0.54

MutPred

0.69

.;Gain of ubiquitination at T38 (P = 0.0162);Gain of ubiquitination at T38 (P = 0.0162);

MVP

0.41

MPC

0.57

ClinPred

0.98

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over