rs759095014

Variant names:

• chr15-40569623-C-G
• rs759095014
• NM_152260.3:c.286C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40569623-C-G
• chr15-40569623-C-T

Variant summary

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

The NM_152260.3(RPUSD2):​c.286C>G​(p.Pro96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,558 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. 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. P96S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RPUSD2 NM_152260.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 1 publications found

Genes affected

RPUSD2 (HGNC:24180): (RNA pseudouridine synthase domain containing 2) Enables pseudouridine synthase activity. Involved in mRNA pseudouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0769251).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152260.3. 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
	RPUSD2	NM_152260.3	MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 1 of 3	NP_689473.1	Q8IZ73-1
	RPUSD2	NM_001286407.2		c.286C>G	p.Pro96Ala	missense	Exon 1 of 3	NP_001273336.1	Q8IZ73-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPUSD2	ENST00000315616.12	TSL:1 MANE Select	c.286C>G	p.Pro96Ala	missense	Exon 1 of 3	ENSP00000323288.7	Q8IZ73-1
	RPUSD2	ENST00000917964.1		c.286C>G	p.Pro96Ala	missense	Exon 1 of 3	ENSP00000588023.1
	RPUSD2	ENST00000559271.1	TSL:2	c.286C>G	p.Pro96Ala	missense	Exon 1 of 3	ENSP00000453036.1	Q8IZ73-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386558 Hom.: 0 Cov.: 29 AF XY: 0.00000147 AC XY: 1 AN XY: 681474

African (AFR) AF: 0.0000312 AC: 1 AN: 32052

American (AMR) AF: 0.00 AC: 0 AN: 35930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22540

East Asian (EAS) AF: 0.00 AC: 0 AN: 37506

South Asian (SAS) AF: 0.00 AC: 0 AN: 75790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073164

Other (OTH) AF: 0.00 AC: 0 AN: 57386

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.0
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.44
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.046
Sift	Uncertain	0.017	D
Sift4G	Benign	0.10	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.28		Loss of glycosylation at P96 (P = 0.0199)
MVP		0.31
MPC		0.23
ClinPred		0.12	T
GERP RS		-0.13
PromoterAI		-0.19	Neutral
Varity_R		0.028
gMVP		0.28
Mutation Taster		=99/1	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: rs759095014; hg19: chr15-40861822;