Variant rs771130284 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001385449.1(RTL9):c.3362C>T(p.Ser1121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,210,245 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000017 ( 0 hom. 7 hem. )

Consequence

RTL9
NM_001385449.1 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

RTL9 (HGNC:29245): (retrotransposon Gag like 9)

RTL9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06985766).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL9	NM_001385449.1 linkuse as main transcript	c.3362C>T	p.Ser1121Leu	missense_variant	3/4	ENST00000520821.6	NP_001372378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RTL9	ENST00000520821.6 linkuse as main transcript	c.3362C>T	p.Ser1121Leu	missense_variant	3/4	4	NM_001385449.1	ENSP00000430395.2	Q8NET4E5RKA1
RTL9	ENST00000465301.2 linkuse as main transcript	c.3362C>T	p.Ser1121Leu	missense_variant	3/4	1		ENSP00000419786.2	Q8NET4
RTL9	ENST00000540313.1 linkuse as main transcript	c.3362C>T	p.Ser1121Leu	missense_variant	1/2	2		ENSP00000441452.1	Q8NET4

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34186

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000940

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182948

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1098207

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363569

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

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:

0.0000190

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000893

AC:

AN:

112038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000940

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spinocerebellar ataxia, X-linked

Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Vavilov Institute of General Genetics RAS, Laboratory of Evolutional Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

T;T

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.039

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.052

B;B

Vest4

0.17

MutPred

0.20

Loss of glycosylation at S1121 (P = 0.0057);Loss of glycosylation at S1121 (P = 0.0057);

MVP

0.068

MPC

0.049

ClinPred

0.27

GERP RS

4.3

Varity_R

0.083

gMVP

0.26

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