X-17800489-C-T

Position:

• chrX-17800489-C-T

Variant summary

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

The NM_021785.6(RAI2):​c.1522G>A​(p.Val508Met) 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. 14/20 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: RAI2 NM_021785.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611

Genes affected

RAI2 (HGNC:9835): (retinoic acid induced 2) Retinoic acid plays a critical role in development, cellular growth, and differentiation. The specific function of this retinoic acid-induced gene has not yet been determined but it may play a role in development. The chromosomal location of this gene designates it to be a candidate for diseases such as Nance-Horan syndrome, sensorineural deafness, non-specific X-linked cognitive disability, oral-facial-digital syndrome, and Fried syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

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=0.093184024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI2	NM_021785.6	c.1522G>A	p.Val508Met	missense_variant	2/2	ENST00000451717.6	NP_068557.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI2	ENST00000451717.6	c.1522G>A	p.Val508Met	missense_variant	2/2	1	NM_021785.6	ENSP00000401323	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

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

Jun 24, 2022

The c.1522G>A (p.V508M) alteration is located in exon 3 (coding exon 1) of the RAI2 gene. This alteration results from a G to A substitution at nucleotide position 1522, causing the valine (V) at amino acid position 508 to be replaced by a methionine (M). 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	0.077
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.013	.;T;T;T;T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T;.;.;.;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.093	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N;N;N
MutationTaster	Benign	0.57	D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.40	N;N;N;N;N
REVEL	Benign	0.027
Sift	Benign	0.32	T;T;T;T;T
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		0.019	.;B;B;B;B
Vest4		0.12
MutPred		0.22		.;Loss of methylation at K507 (P = 0.0168);Loss of methylation at K507 (P = 0.0168);Loss of methylation at K507 (P = 0.0168);Loss of methylation at K507 (P = 0.0168);
MVP		0.91
MPC		0.13
ClinPred		0.087	T
GERP RS		-0.88
Varity_R		0.064
gMVP		0.20

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-17818609;