X-72130447-C-G

Position:

• chrX-72130447-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024455.4(RTL5):​c.1094G>C​(p.Arg365Pro) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RTL5 NM_001024455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.929

Genes affected

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

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]

ACMG classification

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=0.063843876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL5	NM_001405151.1	c.1094G>C	p.Arg365Pro	missense_variant	1/1	ENST00000609883.3	NP_001392080.1
RTL5	NM_001024455.4	c.1094G>C	p.Arg365Pro	missense_variant	1/2		NP_001019626.1
NHSL2	NM_001013627.3	c.281-1632C>G		intron_variant		ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL5	ENST00000609883.3	c.1094G>C	p.Arg365Pro	missense_variant	1/1		NM_001405151.1	ENSP00000476792	P1
NHSL2	ENST00000633930.2	c.281-1632C>G		intron_variant		5	NM_001013627.3	ENSP00000488668	P3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

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

Sep 20, 2023

The c.1094G>C (p.R365P) alteration is located in exon 1 (coding exon 1) of the RGAG4 gene. This alteration results from a G to C substitution at nucleotide position 1094, causing the arginine (R) at amino acid position 365 to be replaced by a proline (P). 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	0.20
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.8
DANN	Benign	0.85
DEOGEN2	Benign	0.0047	T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.20	T
Sift4G	Uncertain	0.026	D
Polyphen		0.76	P
Vest4		0.16
MutPred		0.22		Gain of loop (P = 0.002);
MVP		0.014
ClinPred		0.18	T
GERP RS		-0.13
Varity_R		0.34
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-71350297;