3-23893331-T-A

Variant names:

• chr3-23893331-T-A
• rs1483287759
• NM_020345.4:c.343A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020345.4(NKIRAS1):​c.343A>T​(p.Ile115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: NKIRAS1 NM_020345.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3571002).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020345.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKIRAS1	NM_020345.4	MANE Select	c.343A>T	p.Ile115Phe	missense	Exon 5 of 5	NP_065078.1	Q9NYS0
	NKIRAS1	NM_001377351.1		c.343A>T	p.Ile115Phe	missense	Exon 4 of 4	NP_001364280.1	Q9NYS0
	NKIRAS1	NM_001377352.1		c.343A>T	p.Ile115Phe	missense	Exon 5 of 5	NP_001364281.1	Q9NYS0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKIRAS1	ENST00000425478.7	TSL:1 MANE Select	c.343A>T	p.Ile115Phe	missense	Exon 5 of 5	ENSP00000400385.2	Q9NYS0
	NKIRAS1	ENST00000614374.4	TSL:1	c.343A>T	p.Ile115Phe	missense	Exon 3 of 3	ENSP00000483749.1	Q9NYS0
	NKIRAS1	ENST00000941384.1		c.460A>T	p.Ile154Phe	missense	Exon 6 of 6	ENSP00000611443.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.0000483 AC: 2 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.43
Sift	Benign	0.061	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.19	B
Vest4		0.40
MutPred		0.66		Gain of glycosylation at T114 (P = 0.082)
MVP		0.71
MPC		0.78
ClinPred		0.70	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.75
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1483287759; hg19: chr3-23934822;