chr17-40355358-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000964.4(RARA):c.1108C>T(p.Arg370Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
RARA
NM_000964.4 missense
NM_000964.4 missense
Scores
4
9
5
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
RARA (HGNC:9864): (retinoic acid receptor alpha) This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, RARA
BP4
?
Computational evidence support a benign effect (MetaRNN=0.41900223).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARA | NM_000964.4 | c.1108C>T | p.Arg370Cys | missense_variant | 8/9 | ENST00000254066.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARA | ENST00000254066.10 | c.1108C>T | p.Arg370Cys | missense_variant | 8/9 | 1 | NM_000964.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249668Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135280
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461350Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726954
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.1108C>T (p.R370C) alteration is located in exon 8 (coding exon 7) of the RARA gene. This alteration results from a C to T substitution at nucleotide position 1108, causing the arginine (R) at amino acid position 370 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;D;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;T;D;D
Polyphen
D;D;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0262);Loss of disorder (P = 0.0262);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at