11-126203512-C-T

Position:

chr11-126203512-C-T

Variant summary

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

The NM_032795.3(RPUSD4):c.1040G>A(p.Arg347His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

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: -3.07

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:

RPUSD4 (HGNC:):

RPUSD4 links:

Genome browser will be placed here

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=0.028891832).

BP6

Variant 11-126203512-C-T is Benign according to our data. Variant chr11-126203512-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3315378.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPUSD4	NM_032795.3 linkuse as main transcript	c.1040G>A	p.Arg347His	missense_variant	7/7	ENST00000298317.9	NP_116184.2	Q96CM3-1
RPUSD4	NM_001363516.2 linkuse as main transcript	c.1037G>A	p.Arg346His	missense_variant	7/7		NP_001350445.1
RPUSD4	NM_001144827.2 linkuse as main transcript	c.947G>A	p.Arg316His	missense_variant	7/7		NP_001138299.1	Q96CM3-2
RPUSD4	XM_011543039.3 linkuse as main transcript	c.461G>A	p.Arg154His	missense_variant	5/5		XP_011541341.1	B4DUN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RPUSD4	ENST00000298317.9 linkuse as main transcript	c.1040G>A	p.Arg347His	missense_variant	7/7	1	NM_032795.3	ENSP00000298317.4	Q96CM3-1
RPUSD4	ENST00000533628.5 linkuse as main transcript	c.947G>A	p.Arg316His	missense_variant	7/7	1		ENSP00000433065.1	Q96CM3-2
RPUSD4	ENST00000526942.5 linkuse as main transcript	n.1061G>A		non_coding_transcript_exon_variant	7/7	5
RPUSD4	ENST00000530903.1 linkuse as main transcript	n.1214G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251438

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135906

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:

0.000163

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727246

show subpopulations

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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 05, 2024

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

0.077

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.3

DANN

Benign

0.68

DEOGEN2

Benign

0.0023

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.35

N;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.011

Sift

Benign

0.63

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0020

B;.

Vest4

0.058

MutPred

0.38

Loss of MoRF binding (P = 0.0266);.;

MVP

0.081

MPC

0.19

ClinPred

0.012

GERP RS

-6.2

Varity_R

0.045

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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