Variant 15-49643376-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144955.2(DTWD1):c.713G>A(p.Arg238His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,560,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000077 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DTWD1
NM_001144955.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.75

Variant links:

Genes affected

DTWD1 (HGNC:30926): (DTW domain containing 1) Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTWD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTWD1	NM_001144955.2 linkuse as main transcript	c.713G>A	p.Arg238His	missense_variant	5/5	ENST00000403028.8	NP_001138427.1	Q8N5C7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTWD1	ENST00000403028.8 linkuse as main transcript	c.713G>A	p.Arg238His	missense_variant	5/5	1	NM_001144955.2	ENSP00000385399.3		Q8N5C7-1

Frequencies

GnomAD3 genomes

AF:

0.0000769

AC:

AN:

143012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000731

Gnomad ASJ

AF:

0.000583

Gnomad EAS

AF:

0.000408

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000900

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000773

AC:

AN:

219840

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

119988

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000385

Gnomad ASJ exome

AF:

0.000888

Gnomad EAS exome

AF:

0.0000642

Gnomad SAS exome

AF:

0.0000383

Gnomad FIN exome

AF:

0.0000476

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

152

AN:

1417484

Hom.:

Cov.:

AF XY:

0.0000980

AC XY:

AN XY:

703912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000844

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.000120

GnomAD4 genome

AF:

0.0000769

AC:

AN:

143076

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

AN XY:

68874

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000730

Gnomad4 ASJ

AF:

0.000583

Gnomad4 EAS

AF:

0.000409

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000900

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000188

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.713G>A (p.R238H) alteration is located in exon 6 (coding exon 4) of the DTWD1 gene. This alteration results from a G to A substitution at nucleotide position 713, causing the arginine (R) at amino acid position 238 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

T;T;T

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;.;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Uncertain

-0.044

MutationAssessor

Pathogenic

3.5

H;H;H

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.86

MVP

0.35

MPC

0.33

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.83

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over