Variant 9-124857989-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000348462.6(RPL35):c.301A>C(p.Asn101His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,612,250 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

RPL35
ENST00000348462.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

RPL35 (HGNC:10344): (ribosomal protein L35) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L29P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012282491).

BP6

Variant 9-124857989-T-G is Benign according to our data. Variant chr9-124857989-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 731009.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL35	NM_007209.4 linkuse as main transcript	c.301A>C	p.Asn101His	missense_variant	4/4	ENST00000348462.6	NP_009140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RPL35	ENST00000348462.6 linkuse as main transcript	c.301A>C	p.Asn101His	missense_variant	4/4	1	NM_007209.4	ENSP00000259469	P1
RPL35	ENST00000487431.1 linkuse as main transcript	n.679A>C		non_coding_transcript_exon_variant	3/3	1
RPL35	ENST00000373570.8 linkuse as main transcript	c.*90A>C		3_prime_UTR_variant	5/5	3		ENSP00000362671
RPL35	ENST00000493018.5 linkuse as main transcript	c.*272A>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000437215

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000880

AC:

221

AN:

251194

Hom.:

AF XY:

0.000891

AC XY:

121

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00118

AC:

1721

AN:

1459916

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

833

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00330

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.000958

AC:

146

AN:

152334

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000714

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.000947

AC:

115

EpiCase

AF:

0.000927

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RPL35-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 07, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

0.053

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0058

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.92

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.056

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.052

Polyphen

0.13

Vest4

0.20

MVP

0.67

MPC

1.1

ClinPred

0.037

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.38

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

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