19-5785215-G-T

Position:

• chr19-5785215-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020175.3(DUS3L):​c.1941C>A​(p.Asn647Lys) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUS3L NM_020175.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.186

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS3L	NM_020175.3	c.1941C>A	p.Asn647Lys	missense_variant	13/13	ENST00000309061.12	NP_064560.2
DUS3L	NM_001161619.2	c.1215C>A	p.Asn405Lys	missense_variant	12/12		NP_001155091.1
DUS3L	XM_017027020.2	c.1899C>A	p.Asn633Lys	missense_variant	12/12		XP_016882509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUS3L	ENST00000309061.12	c.1941C>A	p.Asn647Lys	missense_variant	13/13	1	NM_020175.3	ENSP00000311977.5
ENSG00000267157	ENST00000586012.1	c.146+168C>A		intron_variant		3		ENSP00000466514.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 24, 2024

The c.1941C>A (p.N647K) alteration is located in exon 13 (coding exon 13) of the DUS3L gene. This alteration results from a C to A substitution at nucleotide position 1941, causing the asparagine (N) at amino acid position 647 to be replaced by a lysine (K). 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	0.95
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	.;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.97	D;D
Vest4		0.87
MutPred		0.35		.;Gain of MoRF binding (P = 0.0105);
MVP		0.49
MPC		1.4
ClinPred		1.0	D
GERP RS		-3.9
Varity_R		0.81
gMVP		0.84

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: chr19-5785226;