3-9839058-C-T

Variant names:

• chr3-9839058-C-T
• rs770722937
• NM_173659.5:c.814G>A

Variant summary

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

The NM_173659.5(RPUSD3):​c.814G>A​(p.Ala272Thr) 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. 16/22 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. A272S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPUSD3 NM_173659.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09319726).

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.814G>A	p.Ala272Thr	missense	Exon 8 of 9	NP_775930.3	Q6P087-5
	RPUSD3	NM_001142547.3		c.769G>A	p.Ala257Thr	missense	Exon 7 of 8	NP_001136019.2	Q6P087-6
	RPUSD3	NM_001351738.2		c.842G>A	p.Ser281Asn	missense	Exon 8 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.814G>A	p.Ala272Thr	missense	Exon 8 of 9	ENSP00000373331.6	Q6P087-5
	RPUSD3	ENST00000433535.7	TSL:1	c.769G>A	p.Ala257Thr	missense	Exon 7 of 8	ENSP00000398921.3	Q6P087-6
	RPUSD3	ENST00000923702.1		c.940G>A	p.Ala314Thr	missense	Exon 9 of 10	ENSP00000593761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.19
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.35	T
Polyphen		0.65	P
Vest4		0.37
MutPred		0.41		Gain of glycosylation at A280 (P = 0.018)
MVP		0.21
MPC		0.15
ClinPred		0.091	T
GERP RS		2.6
Varity_R		0.030
gMVP		0.42
Mutation Taster		=97/3	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: rs770722937; hg19: chr3-9880742;