rs1555653604

Variant names:

• chr17-42023784-C-G
• NM_017595.6:c.467C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-42023784-C-G
• chr17-42023784-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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 𝑓: 6.8e-7 (0 hom.)
• Consequence: NKIRAS2 NM_017595.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12

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]

ACMG classification

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
NKIRAS2	NM_017595.6	c.467C>G	p.Ser156Cys	missense_variant	Exon 4 of 4	ENST00000393885.9	NP_060065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKIRAS2	ENST00000393885.9	c.467C>G	p.Ser156Cys	missense_variant	Exon 4 of 4	1	NM_017595.6	ENSP00000377463.3

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

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;