5-74770804-G-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014886.6(NSA2):āc.516G>Cā(p.Arg172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,604,194 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 (ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.000048 ( 0 hom. )
Consequence
NSA2
NM_014886.6 missense
NM_014886.6 missense
Scores
7
4
6
Clinical Significance
Conservation
PhyloP100: 1.06
Genes affected
NSA2 (HGNC:30728): (NSA2 ribosome biogenesis factor) This gene encodes a nucleolar protein involved in cell cycle regulation and proliferation. This gene was identified based on sequence similarity to a highly conserved Saccharomyces cerevisiae gene encoding a pre-ribosomal protein, which is involved in large ribosomal subunit biogenesis. The encoded protein is found at elevated levels in diabetic nephropathy. Alternative splicing results in multiple transcript variants. Several related pseudogenes have been identified. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.25278103).
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSA2 | NM_014886.6 | c.516G>C | p.Arg172Ser | missense_variant | 4/6 | ENST00000610426.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSA2 | ENST00000610426.5 | c.516G>C | p.Arg172Ser | missense_variant | 4/6 | 1 | NM_014886.6 | P1 | |
NSA2 | ENST00000296802.9 | c.516G>C | p.Arg172Ser | missense_variant | 4/5 | 5 | |||
NSA2 | ENST00000515524.1 | c.243G>C | p.Arg81Ser | missense_variant | 2/3 | 2 | |||
NSA2 | ENST00000513356.1 | n.614G>C | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000183 AC: 44AN: 240468Hom.: 0 AF XY: 0.000192 AC XY: 25AN XY: 129996
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GnomAD4 exome AF: 0.0000482 AC: 70AN: 1451862Hom.: 0 Cov.: 30 AF XY: 0.0000568 AC XY: 41AN XY: 722010
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74490
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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 | Aug 08, 2022 | The c.516G>C (p.R172S) alteration is located in exon 4 (coding exon 4) of the NSA2 gene. This alteration results from a G to C substitution at nucleotide position 516, causing the arginine (R) at amino acid position 172 to be replaced by a serine (S). 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
Pathogenic
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Polyphen
0.19
.;B
Vest4
MutPred
Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);
MVP
MPC
ClinPred
T
GERP RS
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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