17-17798202-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030665.4(RAI1):​c.5254G>T​(p.Gly1752Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAI1
NM_030665.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21
Variant links:
Genes affected
RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31781253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAI1NM_030665.4 linkc.5254G>T p.Gly1752Trp missense_variant Exon 3 of 6 ENST00000353383.6 NP_109590.3 Q7Z5J4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAI1ENST00000353383.6 linkc.5254G>T p.Gly1752Trp missense_variant Exon 3 of 6 1 NM_030665.4 ENSP00000323074.4 Q7Z5J4-1
RAI1ENST00000583166.1 linkc.-183G>T upstream_gene_variant 2 ENSP00000463984.1 J3QR08

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460266
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
726430
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.010
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T;.
Eigen
Benign
0.0084
Eigen_PC
Benign
-0.029
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.80
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.1
L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0050
D;.
Polyphen
0.96
D;.
Vest4
0.44
MutPred
0.26
Loss of loop (P = 0.0128);.;
MVP
0.10
MPC
1.0
ClinPred
0.99
D
GERP RS
3.6
Varity_R
0.41
gMVP
0.34

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: chr17-17701516; API