chr19-5785501-C-A

Variant names:

• chr19-5785501-C-A
• NM_020175.3:c.1762G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020175.3(DUS3L):​c.1762G>T​(p.Val588Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. V588M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DUS3L NM_020175.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

DUS3L (HGNC:26920): (dihydrouridine synthase 3 like) Enables RNA binding activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267157 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37535384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS3L	NM_020175.3	c.1762G>T	p.Val588Leu	missense_variant	Exon 12 of 13	ENST00000309061.12	NP_064560.2
DUS3L	NM_001161619.2	c.1036G>T	p.Val346Leu	missense_variant	Exon 11 of 12		NP_001155091.1
DUS3L	XM_017027020.2	c.1720G>T	p.Val574Leu	missense_variant	Exon 11 of 12		XP_016882509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUS3L	ENST00000309061.12	c.1762G>T	p.Val588Leu	missense_variant	Exon 12 of 13	1	NM_020175.3	ENSP00000311977.5
ENSG00000267157	ENST00000586012.1	c.28G>T	p.Val10Leu	missense_variant	Exon 2 of 3	3		ENSP00000466514.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412778 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 697666

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: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	.;.;T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	.;D;D
REVEL	Benign	0.18
Sift	Benign	0.074	.;T;T
Sift4G	Benign	0.090	T;T;T
Polyphen		0.040, 0.10	.;B;B
Vest4		0.50, 0.54
MutPred		0.60		.;.;Gain of sheet (P = 0.0477);
MVP		0.26
MPC		0.71
ClinPred		0.92	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5785512;