3-9840238-G-C

Variant names:

• chr3-9840238-G-C
• NM_173659.5:c.646C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173659.5(RPUSD3):​c.646C>G​(p.Arg216Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPUSD3 NM_173659.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPUSD3	NM_173659.5	c.646C>G	p.Arg216Gly	missense_variant	Exon 7 of 9	ENST00000383820.10	NP_775930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPUSD3	ENST00000383820.10	c.646C>G	p.Arg216Gly	missense_variant	Exon 7 of 9	1	NM_173659.5	ENSP00000373331.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	.;T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;M;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.041	D;D;T;D
Polyphen		0.85	P;P;.;.
Vest4		0.57
MutPred		0.70		.;Loss of MoRF binding (P = 0.0144);.;.;
MVP		0.63
MPC		0.66
ClinPred		0.85	D
GERP RS		3.3
Varity_R		0.66
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-9881922;