Variant chrX-72129941-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001024455.4(RTL5):c.1600C>T(p.Arg534Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 1,209,425 control chromosomes in the GnomAD database, including 3 homozygotes. There are 167 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.00040 ( 3 hom. 158 hem. )

Consequence

RTL5
NM_001024455.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.751

Variant links:

Genes affected

RTL5 (HGNC:29430): (retrotransposon Gag like 5)

RTL5 links:

NHSL2 (HGNC:33737): (NHS like 2) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NHSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04572305).

BP6

Variant X-72129941-G-A is Benign according to our data. Variant chrX-72129941-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-72129941-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTL5	NM_001405151.1 linkuse as main transcript	c.1600C>T	p.Arg534Cys	missense_variant	1/1	ENST00000609883.3	NP_001392080.1
RTL5	NM_001024455.4 linkuse as main transcript	c.1600C>T	p.Arg534Cys	missense_variant	1/2		NP_001019626.1
NHSL2	NM_001013627.3 linkuse as main transcript	c.281-2138G>A		intron_variant		ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL5	ENST00000609883.3 linkuse as main transcript	c.1600C>T	p.Arg534Cys	missense_variant	1/1		NM_001405151.1	ENSP00000476792	P1
NHSL2	ENST00000633930.2 linkuse as main transcript	c.281-2138G>A		intron_variant		5	NM_001013627.3	ENSP00000488668	P3	Q5HYW2-1

Frequencies

GnomAD3 genomes

AF:

0.000332

AC:

AN:

111609

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

AN XY:

33771

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.000547

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000392

AC:

AN:

181224

Hom.:

AF XY:

0.000476

AC XY:

AN XY:

67208

show subpopulations

Gnomad AFR exome

AF:

0.0000808

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.0000629

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000395

AC:

434

AN:

1097758

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

158

AN XY:

363190

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000390

Gnomad4 OTH exome

AF:

0.000890

GnomAD4 genome

AF:

0.000331

AC:

AN:

111667

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

AN XY:

33839

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000547

Gnomad4 OTH

AF:

0.00330

Alfa

AF:

0.000666

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000422

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	NHSL2: BS2; RTL5: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0082

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.71

M_CAP

Benign

0.0021

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.15

MVP

0.10

ClinPred

0.023

GERP RS

3.0

Varity_R

0.12

gMVP

0.11

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