chr20-46067161-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_020967.3(NCOA5):c.523C>T(p.Arg175Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
NCOA5
NM_020967.3 missense
NM_020967.3 missense
Scores
8
5
6
Clinical Significance
Conservation
PhyloP100: 6.20
Genes affected
NCOA5 (HGNC:15909): (nuclear receptor coactivator 5) This gene encodes a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCOA5 | NM_020967.3 | c.523C>T | p.Arg175Trp | missense_variant | 5/8 | ENST00000290231.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCOA5 | ENST00000290231.11 | c.523C>T | p.Arg175Trp | missense_variant | 5/8 | 1 | NM_020967.3 | P1 | |
NCOA5 | ENST00000372291.3 | c.208C>T | p.Arg70Trp | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250348Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135334
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461104Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726878
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74310
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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 | Feb 27, 2024 | The c.523C>T (p.R175W) alteration is located in exon 5 (coding exon 4) of the NCOA5 gene. This alteration results from a C to T substitution at nucleotide position 523, causing the arginine (R) at amino acid position 175 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
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