Variant chr3-9840238-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The ENST00000383820.10(RPUSD3):c.646C>T(p.Arg216Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RPUSD3
ENST00000383820.10 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.28

Variant links:

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]

RPUSD3 links:

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]

TTLL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-9840238-G-A is Pathogenic according to our data. Variant chr3-9840238-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225035.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPUSD3	NM_173659.5 linkuse as main transcript	c.646C>T	p.Arg216Cys	missense_variant	7/9	ENST00000383820.10	NP_775930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPUSD3	ENST00000383820.10 linkuse as main transcript	c.646C>T	p.Arg216Cys	missense_variant	7/9	1	NM_173659.5	ENSP00000373331	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251442

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Overall WES conclusion for patient, including all identified alterations: POSSIBLY POSITIVE: Alteration(s) of Uncertain Clinical Significance Detected (Novel Gene) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

.;T;T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

.;M;.;.

MutationTaster

Benign

0.89

N;N;N;D

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.8

D;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.55

MutPred

0.74

.;Loss of MoRF binding (P = 0.0068);.;.;

MVP

0.61

MPC

0.73

ClinPred

0.80

GERP RS

3.3

Varity_R

0.57

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over