rs1555653604

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017595.6(NKIRAS2):​c.467C>G​(p.Ser156Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S156F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NKIRAS2
NM_017595.6 missense

Scores

2
15
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.12
Variant links:
Genes affected
NKIRAS2 (HGNC:17898): (NFKB inhibitor interacting Ras like 2) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; regulation of signal transduction; and surfactant homeostasis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NKIRAS2NM_017595.6 linkc.467C>G p.Ser156Cys missense_variant Exon 4 of 4 ENST00000393885.9 NP_060065.2 Q9NYR9-1A0A024R1Z4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NKIRAS2ENST00000393885.9 linkc.467C>G p.Ser156Cys missense_variant Exon 4 of 4 1 NM_017595.6 ENSP00000377463.3 Q9NYR9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
D;D;.;D;D;.;D
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
.;.;D;.;D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.35
D
MutationAssessor
Uncertain
2.9
M;M;.;M;M;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.2
D;D;.;D;D;.;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0010
D;D;.;D;D;.;D
Sift4G
Uncertain
0.022
D;D;D;D;D;D;T
Polyphen
0.96
P;P;.;P;P;.;.
Vest4
0.29
MutPred
0.62
Loss of phosphorylation at S156 (P = 0.0243);Loss of phosphorylation at S156 (P = 0.0243);.;Loss of phosphorylation at S156 (P = 0.0243);Loss of phosphorylation at S156 (P = 0.0243);.;.;
MVP
0.93
MPC
0.98
ClinPred
0.99
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.48
gMVP
0.66

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: chr17-40175802; API