17-82058249-C-T

Variant names:

• chr17-82058249-C-T
• rs144652762
• NM_022156.5:c.1288G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022156.5(DUS1L):​c.1288G>A​(p.Gly430Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,578,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: DUS1L NM_022156.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• Publications: 2 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]

GPS1 (HGNC:4549): (G protein pathway suppressor 1) This gene is known to suppress G-protein and mitogen-activated signal transduction in mammalian cells. The encoded protein shares significant similarity with Arabidopsis FUS6, which is a regulator of light-mediated signal transduction in plant cells. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084603995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022156.5. 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
	DUS1L	NM_022156.5	MANE Select	c.1288G>A	p.Gly430Arg	missense	Exon 14 of 14	NP_071439.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS1L	ENST00000306796.10	TSL:1 MANE Select	c.1288G>A	p.Gly430Arg	missense	Exon 14 of 14	ENSP00000303515.5	Q6P1R4
	DUS1L	ENST00000354321.11	TSL:1	c.1288G>A	p.Gly430Arg	missense	Exon 13 of 13	ENSP00000346280.7	Q6P1R4
	DUS1L	ENST00000538833.6	TSL:1	c.881G>A	p.Arg294Gln	missense	Exon 10 of 10	ENSP00000445110.2	H0YGW8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152196 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 235814 AF XY: 0.0000234

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 24 AN: 1426292 Hom.: 0 Cov.: 29 AF XY: 0.0000185 AC XY: 13 AN XY: 704164

African (AFR) AF: 0.00 AC: 0 AN: 32426

American (AMR) AF: 0.00 AC: 0 AN: 41850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 38426

South Asian (SAS) AF: 0.0000360 AC: 3 AN: 83304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000184 AC: 20 AN: 1088786

Other (OTH) AF: 0.0000170 AC: 1 AN: 58722

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152314 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.71	N
PhyloP100		3.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.12
Sift	Benign	0.77	T
Sift4G	Benign	0.38	T
Polyphen		0.012	B
Vest4		0.45
MutPred		0.15		Gain of MoRF binding (P = 0.02)
MVP		0.42
MPC		0.15
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.20
gMVP		0.68
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs144652762; hg19: chr17-80016125; COSMIC: COSV57647942; COSMIC: COSV57647942;