17-82061234-G-A

Position:

• chr17-82061234-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022156.5(DUS1L):​c.817C>T​(p.His273Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 9.46

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]

DUS1L (HGNC:):

ACMG classification

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, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS1L	NM_022156.5	c.817C>T	p.His273Tyr	missense_variant	8/14	ENST00000306796.10	NP_071439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUS1L	ENST00000306796.10	c.817C>T	p.His273Tyr	missense_variant	8/14	1	NM_022156.5	ENSP00000303515.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Jan 03, 2022

The c.817C>T (p.H273Y) alteration is located in exon 8 (coding exon 7) of the DUS1L gene. This alteration results from a C to T substitution at nucleotide position 817, causing the histidine (H) at amino acid position 273 to be replaced by a tyrosine (Y). 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	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	31
DANN	Benign	0.96
DEOGEN2	Benign	0.34	T;T;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.7	H;H;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.3	D;D;.
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.042	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.94
MutPred		0.75		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP		0.68
MPC		0.62
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.92

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

LitVar

Other links and lift over

dbSNP: rs2033475213; hg19: chr17-80019110;