chr19-5785453-A-C

Variant names:

• chr19-5785453-A-C
• rs778526477
• NM_020175.3:c.1810T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020175.3(DUS3L):​c.1810T>G​(p.Tyr604Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Y604H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DUS3L NM_020175.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020175.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS3L	NM_020175.3	MANE Select	c.1810T>G	p.Tyr604Asp	missense	Exon 12 of 13	NP_064560.2	Q96G46-1
	DUS3L	NM_001161619.2		c.1084T>G	p.Tyr362Asp	missense	Exon 11 of 12	NP_001155091.1	Q96G46-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS3L	ENST00000309061.12	TSL:1 MANE Select	c.1810T>G	p.Tyr604Asp	missense	Exon 12 of 13	ENSP00000311977.5	Q96G46-1
	DUS3L	ENST00000320699.12	TSL:1	c.1084T>G	p.Tyr362Asp	missense	Exon 11 of 12	ENSP00000315558.7	Q96G46-3
	ENSG00000267157	ENST00000586012.1	TSL:3	c.76T>G	p.Tyr26Asp	missense	Exon 2 of 3	ENSP00000466514.1	K7EMI3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.24
Sift	Benign	0.20	T
Sift4G	Benign	0.16	T
Polyphen		0.11	B
Vest4		0.71
MutPred		0.64		Gain of disorder (P = 0.0111)
MVP		0.57
MPC		1.2
ClinPred		0.84	D
GERP RS		2.5
PromoterAI		0.00090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.83
Mutation Taster		=71/29	polymorphism

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: rs778526477; hg19: chr19-5785464;