Variant X-110451240-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001385449.1(RTL9):c.623T>C(p.Met208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,210,143 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00018 ( 0 hom. 67 hem. )

Consequence

RTL9
NM_001385449.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.13

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012225419).

BP6

Variant X-110451240-T-C is Benign according to our data. Variant chrX-110451240-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2661194.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL9	NM_001385449.1 linkuse as main transcript	c.623T>C	p.Met208Thr	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.623T>C	p.Met208Thr	missense_variant	3/4	4	NM_001385449.1	ENSP00000430395.2	Q8NET4E5RKA1
RTL9	ENST00000465301.2 linkuse as main transcript	c.623T>C	p.Met208Thr	missense_variant	3/4	1		ENSP00000419786.2	Q8NET4
RTL9	ENST00000540313.1 linkuse as main transcript	c.623T>C	p.Met208Thr	missense_variant	1/2	2		ENSP00000441452.1	Q8NET4

Frequencies

GnomAD3 genomes

AF:

0.000411

AC:

AN:

111924

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

AN XY:

34128

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

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:

0.000169

Gnomad OTH

AF:

0.000663

GnomAD3 exomes

AF:

0.000207

AC:

AN:

183373

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67813

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000181

AC:

199

AN:

1098219

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

363573

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000672

GnomAD4 genome

AF:

0.000411

AC:

AN:

111924

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

AN XY:

34128

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.000663

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000476

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000711

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.623T>C (p.M208T) alteration is located in exon 3 (coding exon 1) of the RGAG1 gene. This alteration results from a T to C substitution at nucleotide position 623, causing the methionine (M) at amino acid position 208 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

RTL9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0049

T;T

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.40

.;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.010

Sift

Benign

0.43

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0080

B;B

Vest4

0.30

MVP

0.15

MPC

0.11

ClinPred

0.076

GERP RS

2.9

Varity_R

0.18

gMVP

0.39

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