17-82061262-G-T

Variant names:

• chr17-82061262-G-T
• rs369444572
• NM_022156.5:c.789C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022156.5(DUS1L):​c.789C>A​(p.His263Gln) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUS1L NM_022156.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

Genes affected

DUS1L (HGNC:30086): (dihydrouridine synthase 1 like) Predicted to enable tRNA dihydrouridine synthase activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39602226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS1L	NM_022156.5	c.789C>A	p.His263Gln	missense_variant	Exon 8 of 14	ENST00000306796.10	NP_071439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUS1L	ENST00000306796.10	c.789C>A	p.His263Gln	missense_variant	Exon 8 of 14	1	NM_022156.5	ENSP00000303515.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.789C>A (p.H263Q) alteration is located in exon 8 (coding exon 7) of the DUS1L gene. This alteration results from a C to A substitution at nucleotide position 789, causing the histidine (H) at amino acid position 263 to be replaced by a glutamine (Q). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	.;D;D;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L;.;.
PhyloP100		1.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D;D;.;.
REVEL	Benign	0.15
Sift	Benign	0.042	D;D;.;.
Sift4G	Uncertain	0.018	D;D;D;.
Polyphen		0.082	B;B;.;.
Vest4		0.32
MutPred		0.70		Loss of catalytic residue at R261 (P = 0.0639);Loss of catalytic residue at R261 (P = 0.0639);Loss of catalytic residue at R261 (P = 0.0639);.;
MVP		0.38
MPC		0.14
ClinPred		0.85	D
GERP RS		5.0
PromoterAI		0.013	Neutral
Varity_R		0.28
gMVP		0.71

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

Other links and lift over

dbSNP: rs369444572; hg19: chr17-80019138;