chr14-23476289-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001042635.2(NGDN):c.595C>T(p.Arg199Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,614,092 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 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
NGDN
NM_001042635.2 missense
NM_001042635.2 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 0.868
Genes affected
NGDN (HGNC:20271): (neuroguidin) Neuroguidin is an EIF4E (MIM 133440)-binding protein that interacts with CPEB (MIM 607342) and functions as a translational regulatory protein during development of the vertebrate nervous system (Jung et al., 2006 [PubMed 16705177]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050338417).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NGDN | NM_001042635.2 | c.595C>T | p.Arg199Trp | missense_variant | 8/11 | ENST00000408901.8 | NP_001036100.1 | |
NGDN | NM_015514.2 | c.595C>T | p.Arg199Trp | missense_variant | 8/10 | NP_056329.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NGDN | ENST00000408901.8 | c.595C>T | p.Arg199Trp | missense_variant | 8/11 | 1 | NM_001042635.2 | ENSP00000386134.3 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251246Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135782
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GnomAD4 exome AF: 0.000206 AC: 301AN: 1461862Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 156AN XY: 727234
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74422
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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 24, 2023 | The c.595C>T (p.R199W) alteration is located in exon 8 (coding exon 8) of the NGDN gene. This alteration results from a C to T substitution at nucleotide position 595, causing the arginine (R) at amino acid position 199 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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