Variant X-110451507-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001385449.1(RTL9):c.890C>T(p.Pro297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000728 in 1,098,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 24)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

RTL9
NM_001385449.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.215

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037371784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL9	NM_001385449.1 linkuse as main transcript	c.890C>T	p.Pro297Leu	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.890C>T	p.Pro297Leu	missense_variant	3/4	4	NM_001385449.1	ENSP00000430395.2	Q8NET4E5RKA1
RTL9	ENST00000465301.2 linkuse as main transcript	c.890C>T	p.Pro297Leu	missense_variant	3/4	1		ENSP00000419786.2	Q8NET4
RTL9	ENST00000540313.1 linkuse as main transcript	c.890C>T	p.Pro297Leu	missense_variant	1/2	2		ENSP00000441452.1	Q8NET4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183369

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67811

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098205

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363559

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:

0.00000713

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

May 26, 2024

The c.890C>T (p.P297L) alteration is located in exon 3 (coding exon 1) of the RGAG1 gene. This alteration results from a C to T substitution at nucleotide position 890, causing the proline (P) at amino acid position 297 to be replaced by a leucine (L). 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

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.19

DANN

Benign

0.37

DEOGEN2

Benign

0.0044

T;T

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.034

Sift

Benign

0.42

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.63

P;P

Vest4

0.024

MutPred

0.21

Loss of phosphorylation at T296 (P = 0.0725);Loss of phosphorylation at T296 (P = 0.0725);

MVP

0.043

MPC

0.055

ClinPred

0.085

GERP RS

-1.9

Varity_R

0.030

gMVP

0.46

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