Variant chr11-126205474-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032795.3(RPUSD4):c.790A>G(p.Ile264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPUSD4
NM_032795.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.965

Variant links:

Genes affected

RPUSD4 (HGNC:25898): (RNA pseudouridine synthase D4) Enables mitochondrial ribosomal large subunit rRNA binding activity; pseudouridine synthase activity; and tRNA binding activity. Involved in mitochondrial tRNA pseudouridine synthesis and positive regulation of mitochondrial translation. Located in mitochondrion; nucleoplasm; and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]

RPUSD4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024258703).

BP6

Variant 11-126205474-T-C is Benign according to our data. Variant chr11-126205474-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2294686.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPUSD4	NM_032795.3 linkuse as main transcript	c.790A>G	p.Ile264Val	missense_variant	5/7	ENST00000298317.9
RPUSD4	NM_001363516.2 linkuse as main transcript	c.790A>G	p.Ile264Val	missense_variant	5/7
RPUSD4	NM_001144827.2 linkuse as main transcript	c.697A>G	p.Ile233Val	missense_variant	5/7
RPUSD4	XM_011543039.3 linkuse as main transcript	c.211A>G	p.Ile71Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPUSD4	ENST00000298317.9 linkuse as main transcript	c.790A>G	p.Ile264Val	missense_variant	5/7	1	NM_032795.3	P1	Q96CM3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251242

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.67

DANN

Benign

0.53

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.23

M_CAP

Benign

0.0037

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

1.4

REVEL

Benign

0.026

Sift

Benign

0.17

Sift4G

Benign

0.089

MutPred

0.25

Gain of MoRF binding (P = 4e-04);

MVP

0.085

ClinPred

0.088

GERP RS

-6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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