chr5-74770664-G-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_014886.6(NSA2):c.376G>T(p.Ala126Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000961 in 1,456,508 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
NSA2
NM_014886.6 missense
NM_014886.6 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 9.43
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 -4 ACMG points.
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSA2 | NM_014886.6 | c.376G>T | p.Ala126Ser | missense_variant | 4/6 | ENST00000610426.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSA2 | ENST00000610426.5 | c.376G>T | p.Ala126Ser | missense_variant | 4/6 | 1 | NM_014886.6 | P1 | |
NSA2 | ENST00000296802.9 | c.376G>T | p.Ala126Ser | missense_variant | 4/5 | 5 | |||
NSA2 | ENST00000515524.1 | c.103G>T | p.Ala35Ser | missense_variant | 2/3 | 2 | |||
NSA2 | ENST00000513356.1 | n.474G>T | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246632Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133228
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GnomAD4 exome AF: 0.00000961 AC: 14AN: 1456508Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9AN XY: 724388
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
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2
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 | Jun 26, 2023 | The c.376G>T (p.A126S) alteration is located in exon 4 (coding exon 4) of the NSA2 gene. This alteration results from a G to T substitution at nucleotide position 376, causing the alanine (A) at amino acid position 126 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
MutPred
Gain of phosphorylation at A126 (P = 0.0346);Gain of phosphorylation at A126 (P = 0.0346);
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