3-9840277-C-G

Variant names:

• chr3-9840277-C-G
• rs745877910
• NM_173659.5:c.607G>C

Variant summary

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

The NM_173659.5(RPUSD3):​c.607G>C​(p.Asp203His) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: RPUSD3 NM_173659.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

RPUSD3 (HGNC:28437): (RNA pseudouridine synthase D3) This gene encodes a protein that functions in the assembly of the mitochondrial ribosome by adding a pseudouridine group to 16S rRNA. Loss of this gene results in causes defects in mitochondrial protein production. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

TTLL3 (HGNC:24483): (tubulin tyrosine ligase like 3) Enables protein-glycine ligase activity. Predicted to be involved in axoneme assembly and flagellated sperm motility. Predicted to be located in axoneme; microtubule cytoskeleton; and sperm flagellum. [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=0.40926874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173659.5. 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
	RPUSD3	NM_173659.5	MANE Select	c.607G>C	p.Asp203His	missense	Exon 7 of 9	NP_775930.3	Q6P087-5
	RPUSD3	NM_001142547.3		c.562G>C	p.Asp188His	missense	Exon 6 of 8	NP_001136019.2	Q6P087-6
	RPUSD3	NM_001351738.2		c.635G>C	p.Gly212Ala	missense	Exon 7 of 9	NP_001338667.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPUSD3	ENST00000383820.10	TSL:1 MANE Select	c.607G>C	p.Asp203His	missense	Exon 7 of 9	ENSP00000373331.6	Q6P087-5
	RPUSD3	ENST00000433535.7	TSL:1	c.562G>C	p.Asp188His	missense	Exon 6 of 8	ENSP00000398921.3	Q6P087-6
	RPUSD3	ENST00000923702.1		c.733G>C	p.Asp245His	missense	Exon 8 of 10	ENSP00000593761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.26
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	0.099
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.66		Gain of MoRF binding (P = 0.0365)
MVP		0.68
MPC		0.60
ClinPred		0.77	D
GERP RS		3.3
PromoterAI		0.0062	Neutral
Varity_R		0.079
gMVP		0.63
Mutation Taster		=85/15	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: rs745877910; hg19: chr3-9881961;