X-135032715-A-G

Variant names:

• chrX-135032715-A-G
• NM_001078171.2:c.332A>G

Variant summary

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

The NM_001078171.2(RTL8C):​c.332A>G​(p.Glu111Gly) 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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: RTL8C NM_001078171.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

Genes affected

RTL8C (HGNC:2569): (retrotransposon Gag like 8C) Predicted to be located in plasma membrane. [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=0.12479907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTL8C	NM_001078171.2	c.332A>G	p.Glu111Gly	missense_variant	Exon 1 of 1	ENST00000257013.9	NP_001071639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL8C	ENST00000257013.9	c.332A>G	p.Glu111Gly	missense_variant	Exon 1 of 1	6	NM_001078171.2	ENSP00000257013.7
RTL8C	ENST00000464369.1	n.194+140A>G		intron_variant	Intron 1 of 1	5
RTL8C	ENST00000495563.5	n.194+140A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332A>G (p.E111G) alteration is located in exon 1 (coding exon 1) of the FAM127A gene. This alteration results from a A to G substitution at nucleotide position 332, causing the glutamic acid (E) at amino acid position 111 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.090	T
Polyphen		0.68	P
Vest4		0.27
MutPred		0.20		Loss of solvent accessibility (P = 0.0387);
MVP		0.082
MPC		2.5
ClinPred		0.91	D
GERP RS		3.7
gMVP		0.89

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-134166745;