3-158732207-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_206963.2(RARRES1):c.209T>A(p.Phe70Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RARRES1
NM_206963.2 missense
NM_206963.2 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.07
Genes affected
RARRES1 (HGNC:9867): (retinoic acid receptor responder 1) This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island. Alternatively spliced transcript variant encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
MFSD1 (HGNC:25874): (major facilitator superfamily domain containing 1) Predicted to enable protein homodimerization activity. Predicted to be involved in protein localization to lysosome and protein stabilization. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
RARRES1 | NM_206963.2 | c.209T>A | p.Phe70Tyr | missense_variant | 1/6 | ENST00000237696.10 | NP_996846.1 | |
RARRES1 | NM_002888.4 | c.209T>A | p.Phe70Tyr | missense_variant | 1/4 | NP_002879.2 | ||
RARRES1 | XM_005247686.6 | c.209T>A | p.Phe70Tyr | missense_variant | 1/6 | XP_005247743.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RARRES1 | ENST00000237696.10 | c.209T>A | p.Phe70Tyr | missense_variant | 1/6 | 1 | NM_206963.2 | ENSP00000237696 | P1 | |
RARRES1 | ENST00000479756.1 | c.209T>A | p.Phe70Tyr | missense_variant | 1/4 | 1 | ENSP00000418556 | |||
MFSD1 | ENST00000486568.5 | c.-207A>T | 5_prime_UTR_variant | 1/5 | 4 | ENSP00000417414 | ||||
RARRES1 | ENST00000498640.1 | n.283T>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1267890Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0AN XY: 622660
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151996Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74242
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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 | May 05, 2023 | The c.209T>A (p.F70Y) alteration is located in exon 1 (coding exon 1) of the RARRES1 gene. This alteration results from a T to A substitution at nucleotide position 209, causing the phenylalanine (F) at amino acid position 70 to be replaced by a tyrosine (Y). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0914);Gain of MoRF binding (P = 0.0914);
MVP
MPC
ClinPred
D
GERP RS
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