X-110451803-G-A

Position:

• chrX-110451803-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385449.1(RTL9):​c.1186G>A​(p.Gly396Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RTL9 NM_001385449.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.492

Genes affected

RTL9 (HGNC:29245): (retrotransposon Gag like 9)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1396198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL9	NM_001385449.1	c.1186G>A	p.Gly396Arg	missense_variant	3/4	ENST00000520821.6	NP_001372378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL9	ENST00000520821.6	c.1186G>A	p.Gly396Arg	missense_variant	3/4	4	NM_001385449.1	ENSP00000430395	P1
RTL9	ENST00000465301.2	c.1186G>A	p.Gly396Arg	missense_variant	3/4	1		ENSP00000419786	P1
RTL9	ENST00000540313.1	c.1186G>A	p.Gly396Arg	missense_variant	1/2	2		ENSP00000441452	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2023

The c.1186G>A (p.G396R) 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 1186, causing the glycine (G) at amino acid position 396 to be replaced by an arginine (R). 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	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;T
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.072
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		1.0	D;D
Vest4		0.075
MutPred		0.28		Gain of MoRF binding (P = 0.0162);Gain of MoRF binding (P = 0.0162);
MVP		0.068
MPC		0.065
ClinPred		0.84	D
GERP RS		-0.70
Varity_R		0.14
gMVP		0.52

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

Other links and lift over

dbSNP: rs2068943219; hg19: chrX-109695031;