19-45914534-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001029861.3(NANOS2):​c.160G>A​(p.Gly54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

NANOS2
NM_001029861.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39
Variant links:
Genes affected
NANOS2 (HGNC:23292): (nanos C2HC-type zinc finger 2) Predicted to enable mRNA binding activity. Involved in negative regulation of translation and positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.17127356).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NANOS2NM_001029861.3 linkc.160G>A p.Gly54Arg missense_variant Exon 1 of 1 ENST00000341294.4 NP_001025032.1 P60321

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NANOS2ENST00000341294.4 linkc.160G>A p.Gly54Arg missense_variant Exon 1 of 1 6 NM_001029861.3 ENSP00000341021.2 P60321

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.160G>A (p.G54R) alteration is located in exon 1 (coding exon 1) of the NANOS2 gene. This alteration results from a G to A substitution at nucleotide position 160, causing the glycine (G) at amino acid position 54 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
0.15
N
REVEL
Benign
0.098
Sift
Benign
0.22
T
Sift4G
Benign
0.48
T
Polyphen
0.87
P
Vest4
0.18
MutPred
0.28
Gain of solvent accessibility (P = 0.0014);
MVP
0.043
MPC
1.3
ClinPred
0.62
D
GERP RS
4.6
Varity_R
0.066
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-46417792; API