Variant X-110451616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001385449.1(RTL9):c.999G>A(p.Met333Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000388 in 1,209,945 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000040 ( 0 hom. 12 hem. )

Consequence

RTL9
NM_001385449.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.300

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014217675).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL9	NM_001385449.1 linkuse as main transcript	c.999G>A	p.Met333Ile	missense_variant	3/4	ENST00000520821.6	NP_001372378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RTL9	ENST00000520821.6 linkuse as main transcript	c.999G>A	p.Met333Ile	missense_variant	3/4	4	NM_001385449.1	ENSP00000430395	P1
RTL9	ENST00000465301.2 linkuse as main transcript	c.999G>A	p.Met333Ile	missense_variant	3/4	1		ENSP00000419786	P1
RTL9	ENST00000540313.1 linkuse as main transcript	c.999G>A	p.Met333Ile	missense_variant	1/2	2		ENSP00000441452	P1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33894

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183415

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67857

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1098247

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363601

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000451

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33894

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.999G>A (p.M333I) alteration is located in exon 3 (coding exon 1) of the RGAG1 gene. This alteration results from a G to A substitution at nucleotide position 999, causing the methionine (M) at amino acid position 333 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

DANN

Benign

0.92

DEOGEN2

Benign

0.0027

T;T

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0080

B;B

Vest4

0.10

MutPred

0.17

Gain of phosphorylation at T335 (P = 0.0918);Gain of phosphorylation at T335 (P = 0.0918);

MVP

0.068

MPC

0.056

ClinPred

0.037

GERP RS

1.8

Varity_R

0.13

gMVP

0.37

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