Variant X-17800972-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_021785.6(RAI2):c.1039G>C(p.Val347Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

RAI2
NM_021785.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.662

Variant links:

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]

RAI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04226926).

BP6

Variant X-17800972-C-G is Benign according to our data. Variant chrX-17800972-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2249759.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI2	NM_021785.6 linkuse as main transcript	c.1039G>C	p.Val347Leu	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 linkuse as main transcript	c.1039G>C	p.Val347Leu	missense_variant	2/2	1	NM_021785.6	ENSP00000401323	P1	Q9Y5P3-1

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111339

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33523

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183061

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67537

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097824

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000898

AC:

AN:

111339

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33523

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.3

DANN

Benign

0.73

DEOGEN2

Benign

0.026

.;T;T;T;T

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.61

T;.;.;.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.7

.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.53

N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;B;B;B;B

Vest4

0.061

MutPred

0.15

.;Gain of glycosylation at S346 (P = 0.0593);Gain of glycosylation at S346 (P = 0.0593);Gain of glycosylation at S346 (P = 0.0593);Gain of glycosylation at S346 (P = 0.0593);

MVP

0.80

MPC

0.13

ClinPred

0.016

GERP RS

2.5

Varity_R

0.061

gMVP

0.082

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over