chr1-224308091-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002533.4(NVL):c.515G>A(p.Gly172Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,612,050 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
NVL
NM_002533.4 missense
NM_002533.4 missense
Scores
2
8
7
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
NVL (HGNC:8070): (nuclear VCP like) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. Two encoded proteins, described as major and minor isoforms, have been localized to distinct regions of the nucleus. The largest encoded protein (major isoform) has been localized to the nucleolus and shown to participate in ribosome biosynthesis (PMID: 15469983, 16782053), while the minor isoform has been localized to the nucleoplasmin. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12852108).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NVL | NM_002533.4 | c.515G>A | p.Gly172Glu | missense_variant | 6/23 | ENST00000281701.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NVL | ENST00000281701.11 | c.515G>A | p.Gly172Glu | missense_variant | 6/23 | 1 | NM_002533.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000883 AC: 22AN: 249276Hom.: 0 AF XY: 0.0000891 AC XY: 12AN XY: 134684
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1459742Hom.: 0 Cov.: 29 AF XY: 0.0000358 AC XY: 26AN XY: 726140
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74480
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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 27, 2021 | The c.515G>A (p.G172E) alteration is located in exon 6 (coding exon 6) of the NVL gene. This alteration results from a G to A substitution at nucleotide position 515, causing the glycine (G) at amino acid position 172 to be replaced by a glutamic acid (E). 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
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;D
Sift4G
Benign
T;T;.;D
Polyphen
0.99
.;D;.;.
Vest4
MutPred
0.19
.;Loss of helix (P = 0.0558);.;.;
MVP
MPC
0.37
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