15-49632180-A-G

Position:

• chr15-49632180-A-G

Variant summary

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

The NM_001144955.2(DTWD1):​c.286A>G​(p.Ile96Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTWD1 NM_001144955.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20

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 (HGNC:):

ACMG classification

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	c.286A>G	p.Ile96Val	missense_variant	3/5	ENST00000403028.8	NP_001138427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTWD1	ENST00000403028.8	c.286A>G	p.Ile96Val	missense_variant	3/5	1	NM_001144955.2	ENSP00000385399.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.286A>G (p.I96V) alteration is located in exon 4 (coding exon 2) of the DTWD1 gene. This alteration results from a A to G substitution at nucleotide position 286, causing the isoleucine (I) at amino acid position 96 to be replaced by a valine (V). 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	Benign	0.21
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.065	T;T;.;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M;M;.;.;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.85	N;N;N;N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;T;T;D
Sift4G	Benign	0.096	T;T;D;D;T
Polyphen		1.0	D;D;.;.;D
Vest4		0.73
MutPred		0.81		Loss of methylation at K92 (P = 0.1349);Loss of methylation at K92 (P = 0.1349);Loss of methylation at K92 (P = 0.1349);.;Loss of methylation at K92 (P = 0.1349);
MVP		0.088
MPC		0.24
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-49924377;