Variant chrX-72129904-C-T 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_001024455.4(RTL5):c.1637G>A(p.Arg546His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,096,876 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

RTL5
NM_001024455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09946433).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTL5	NM_001405151.1 linkuse as main transcript	c.1637G>A	p.Arg546His	missense_variant	1/1	ENST00000609883.3	NP_001392080.1
RTL5	NM_001024455.4 linkuse as main transcript	c.1637G>A	p.Arg546His	missense_variant	1/2		NP_001019626.1
NHSL2	NM_001013627.3 linkuse as main transcript	c.281-2175C>T		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.1637G>A	p.Arg546His	missense_variant	1/1		NM_001405151.1	ENSP00000476792	P1
NHSL2	ENST00000633930.2 linkuse as main transcript	c.281-2175C>T		intron_variant		5	NM_001013627.3	ENSP00000488668	P3	Q5HYW2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000223

AC:

AN:

179244

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

65364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000734

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:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1096876

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000853

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:

0.00000951

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000579

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

Dec 26, 2023

The c.1637G>A (p.R546H) alteration is located in exon 1 (coding exon 1) of the RGAG4 gene. This alteration results from a G to A substitution at nucleotide position 1637, causing the arginine (R) at amino acid position 546 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0033

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

M_CAP

Benign

0.0044

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.58

Sift4G

Uncertain

0.060

Polyphen

0.99

Vest4

0.23

MutPred

0.30

Loss of glycosylation at P547 (P = 0.0655);

MVP

0.17

ClinPred

0.14

GERP RS

3.1

Varity_R

0.070

gMVP

0.096

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