X-72130787-C-T

Position:

• chrX-72130787-C-T

Variant summary

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

The NM_001024455.4(RTL5):​c.754G>A​(p.Gly252Ser) 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. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RTL5 NM_001024455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.474

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 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=0.16089883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL5	NM_001405151.1	c.754G>A	p.Gly252Ser	missense_variant	1/1	ENST00000609883.3	NP_001392080.1
RTL5	NM_001024455.4	c.754G>A	p.Gly252Ser	missense_variant	1/2		NP_001019626.1
NHSL2	NM_001013627.3	c.281-1292C>T		intron_variant		ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL5	ENST00000609883.3	c.754G>A	p.Gly252Ser	missense_variant	1/1		NM_001405151.1	ENSP00000476792	P1
NHSL2	ENST00000633930.2	c.281-1292C>T		intron_variant		5	NM_001013627.3	ENSP00000488668	P3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

RTL5: PM2, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.99	D;N;N
PrimateAI	Benign	0.38	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.51	P
Vest4		0.17
MutPred		0.41		Gain of helix (P = 0.0854);
MVP		0.32
ClinPred		0.97	D
GERP RS		1.4
Varity_R		0.10
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-71350637;