8-28023405-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001010906.2(NUGGC):c.2303C>T(p.Ala768Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
NUGGC
NM_001010906.2 missense
NM_001010906.2 missense
Scores
3
4
12
Clinical Significance
Conservation
PhyloP100: 4.47
Genes affected
NUGGC (HGNC:33550): (nuclear GTPase, germinal center associated) Enables GTPase activity. Involved in cellular response to lipopolysaccharide; negative regulation of apoptotic process; and regulation of nuclear cell cycle DNA replication. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40316126).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NUGGC | NM_001010906.2 | c.2303C>T | p.Ala768Val | missense_variant | 19/19 | ENST00000413272.7 | NP_001010906.1 | |
NUGGC | XM_011544523.3 | c.2375C>T | p.Ala792Val | missense_variant | 19/19 | XP_011542825.1 | ||
NUGGC | XM_011544524.4 | c.2375C>T | p.Ala792Val | missense_variant | 19/19 | XP_011542826.1 | ||
NUGGC | XM_011544525.2 | c.1142C>T | p.Ala381Val | missense_variant | 11/11 | XP_011542827.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NUGGC | ENST00000413272.7 | c.2303C>T | p.Ala768Val | missense_variant | 19/19 | 5 | NM_001010906.2 | ENSP00000408697.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248932Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135052
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461652Hom.: 0 Cov.: 33 AF XY: 0.0000371 AC XY: 27AN XY: 727114
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
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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 | Sep 25, 2024 | The c.2303C>T (p.A768V) alteration is located in exon 19 (coding exon 18) of the NUGGC gene. This alteration results from a C to T substitution at nucleotide position 2303, causing the alanine (A) at amino acid position 768 to be replaced by a valine (V). 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
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R772 (P = 0.1148);
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