chrX-72130447-C-G

Variant names:

• chrX-72130447-C-G
• rs755935647
• NM_001405151.1:c.1094G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001405151.1(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. 12/17 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_001405151.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.929
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063843876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405151.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL5	NM_001405151.1	MANE Select	c.1094G>C	p.Arg365Pro	missense	Exon 1 of 1	NP_001392080.1	Q5HYW3
	NHSL2	NM_001013627.3	MANE Select	c.281-1632C>G		intron	N/A	NP_001013649.2	Q5HYW2-1
	RTL5	NM_001024455.4		c.1094G>C	p.Arg365Pro	missense	Exon 1 of 2	NP_001019626.1	Q5HYW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL5	ENST00000609883.3	TSL:6 MANE Select	c.1094G>C	p.Arg365Pro	missense	Exon 1 of 1	ENSP00000476792.1	Q5HYW3
	NHSL2	ENST00000633930.2	TSL:5 MANE Select	c.281-1632C>G		intron	N/A	ENSP00000488668.1	Q5HYW2-1
	RTL5	ENST00000479991.1	TSL:1	n.1094G>C		non_coding_transcript_exon	Exon 1 of 2	ENSP00000418667.1	Q5HYW3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.93
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs755935647; hg19: chrX-71350297;