15-57438700-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032866.5(CGNL1):c.701G>A(p.Cys234Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CGNL1
NM_032866.5 missense
NM_032866.5 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 4.60
Genes affected
CGNL1 (HGNC:25931): (cingulin like 1) This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]
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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 | UniProt |
---|---|---|---|---|---|---|---|
CGNL1 | NM_032866.5 | c.701G>A | p.Cys234Tyr | missense_variant | 2/19 | ENST00000281282.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CGNL1 | ENST00000281282.6 | c.701G>A | p.Cys234Tyr | missense_variant | 2/19 | 1 | NM_032866.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251300Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135832
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727248
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
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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 | Jan 04, 2022 | The c.701G>A (p.C234Y) alteration is located in exon 2 (coding exon 1) of the CGNL1 gene. This alteration results from a G to A substitution at nucleotide position 701, causing the cysteine (C) at amino acid position 234 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.0166);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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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