rs193920771

Variant names:

• chr16-786368-T-C
• rs193920771
• NM_058192.3:c.521A>G
• RPUSD1 p.His174Arg

Your query was ambiguous. Multiple possible variants found:

• chr16-786368-T-C
• chr16-786368-T-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_058192.3(RPUSD1):​c.521A>G​(p.His174Arg) variant causes a missense change. 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 (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RPUSD1 NM_058192.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.11
• Publications: 3 publications found

Genes affected

RPUSD1 (HGNC:14173): (RNA pseudouridine synthase domain containing 1) Predicted to enable pseudouridine synthase activity. Predicted to be involved in enzyme-directed rRNA pseudouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058192.3. 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
	RPUSD1	NM_058192.3	MANE Select	c.521A>G	p.His174Arg	missense	Exon 6 of 6	NP_478072.1	Q9UJJ7
	RPUSD1	NM_001324086.2		c.530A>G	p.His177Arg	missense	Exon 6 of 6	NP_001311015.1
	RPUSD1	NM_001369658.1		c.473A>G	p.His158Arg	missense	Exon 6 of 6	NP_001356587.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPUSD1	ENST00000007264.7	TSL:2 MANE Select	c.521A>G	p.His174Arg	missense	Exon 6 of 6	ENSP00000007264.2	Q9UJJ7
	RPUSD1	ENST00000561734.5	TSL:1	c.521A>G	p.His174Arg	missense	Exon 5 of 5	ENSP00000455026.1	Q9UJJ7
	RPUSD1	ENST00000918138.1		c.521A>G	p.His174Arg	missense	Exon 6 of 6	ENSP00000588197.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.81
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.082	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		6.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.95

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193920771;

hg19: chr16-836368;

COSMIC: COSV50102965;

COSMIC: COSV50102965;