X-17800854-A-G

Position:

• chrX-17800854-A-G

Variant summary

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

The NM_021785.6(RAI2):​c.1157T>C​(p.Phe386Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RAI2 NM_021785.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.09

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI2	NM_021785.6	c.1157T>C	p.Phe386Ser	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.1157T>C	p.Phe386Ser	missense_variant	2/2	1	NM_021785.6	ENSP00000401323	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

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

Oct 29, 2021

The c.1157T>C (p.F386S) alteration is located in exon 3 (coding exon 1) of the RAI2 gene. This alteration results from a T to C substitution at nucleotide position 1157, causing the phenylalanine (F) at amino acid position 386 to be replaced by a serine (S). 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	0.19
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T;T;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.48	T;.;.;.;T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	.;L;L;L;L
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.4	D;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		0.99	.;D;D;D;D
Vest4		0.67
MutPred		0.24		.;Gain of glycosylation at F386 (P = 0.0059);Gain of glycosylation at F386 (P = 0.0059);Gain of glycosylation at F386 (P = 0.0059);Gain of glycosylation at F386 (P = 0.0059);
MVP		0.74
MPC		0.24
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.38
gMVP		0.28

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-17818974;