chr3-23893169-A-G

Variant names:

• chr3-23893169-A-G
• rs1375608897
• NM_020345.4:c.505T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020345.4(NKIRAS1):​c.505T>C​(p.Ser169Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NKIRAS1 NM_020345.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) 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; lung alveolus development; and surfactant homeostasis. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38505068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKIRAS1	NM_020345.4	c.505T>C	p.Ser169Pro	missense_variant	Exon 5 of 5	ENST00000425478.7	NP_065078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKIRAS1	ENST00000425478.7	c.505T>C	p.Ser169Pro	missense_variant	Exon 5 of 5	1	NM_020345.4	ENSP00000400385.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248816 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134446

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459442 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725830

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;D;D;D;D;D;D;D
Eigen	Benign	0.11
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	.;.;.;.;T;.;.;T;.
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.7	L;L;L;L;L;.;.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N;N;N;N;.;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.16	T;T;T;T;.;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T;T
Polyphen		0.51	P;P;P;P;P;P;P;P;P
Vest4		0.38
MutPred		0.43		Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);Gain of glycosylation at S173 (P = 0.0115);
MVP		0.78
MPC		0.95
ClinPred		0.57	D
GERP RS		3.6
Varity_R		0.28
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1375608897; hg19: chr3-23934660;