15-40569887-G-A

Variant names:

• chr15-40569887-G-A
• NM_152260.3:c.550G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152260.3(RPUSD2):​c.550G>A​(p.Ala184Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPUSD2 NM_152260.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2852037).

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.550G>A	p.Ala184Thr	missense	Exon 1 of 3	NP_689473.1	Q8IZ73-1
	RPUSD2	NM_001286407.2		c.423+127G>A		intron	N/A	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.550G>A	p.Ala184Thr	missense	Exon 1 of 3	ENSP00000323288.7	Q8IZ73-1
	RPUSD2	ENST00000917964.1		c.550G>A	p.Ala184Thr	missense	Exon 1 of 3	ENSP00000588023.1
	RPUSD2	ENST00000890562.1		c.550G>A	p.Ala184Thr	missense	Exon 1 of 2	ENSP00000560621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1433478 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 710666

African (AFR) AF: 0.00 AC: 0 AN: 33118

American (AMR) AF: 0.00 AC: 0 AN: 40074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25586

East Asian (EAS) AF: 0.00 AC: 0 AN: 38680

South Asian (SAS) AF: 0.00 AC: 0 AN: 82548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098660

Other (OTH) AF: 0.00 AC: 0 AN: 59312

GnomAD4 genome Cov.: 33

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	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.041
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.039
Sift	Benign	0.45	T
Sift4G	Benign	0.54	T
Polyphen		0.0080	B
Vest4		0.46
MutPred		0.29		Loss of methylation at R183 (P = 0.0948)
MVP		0.50
MPC		0.51
ClinPred		0.97	D
GERP RS		4.9
PromoterAI		0.030	Neutral
Varity_R		0.21
gMVP		0.48

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

hg19: chr15-40862086;