3-23900906-C-T

Variant names:

• chr3-23900906-C-T
• NM_020345.4:c.238G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020345.4(NKIRAS1):​c.238G>A​(p.Asp80Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NKIRAS1 NM_020345.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

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.238G>A	p.Asp80Asn	missense	Exon 4 of 5	NP_065078.1	Q9NYS0
	NKIRAS1	NM_001377351.1		c.238G>A	p.Asp80Asn	missense	Exon 3 of 4	NP_001364280.1	Q9NYS0
	NKIRAS1	NM_001377352.1		c.238G>A	p.Asp80Asn	missense	Exon 4 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.238G>A	p.Asp80Asn	missense	Exon 4 of 5	ENSP00000400385.2	Q9NYS0
	NKIRAS1	ENST00000614374.4	TSL:1	c.238G>A	p.Asp80Asn	missense	Exon 2 of 3	ENSP00000483749.1	Q9NYS0
	NKIRAS1	ENST00000941384.1		c.238G>A	p.Asp80Asn	missense	Exon 4 of 6	ENSP00000611443.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.081	T
Polyphen		1.0	D
Vest4		0.84
MutPred		0.66		Loss of stability (P = 0.0527)
MVP		0.91
MPC		1.2
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.67
gMVP		0.81
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr3-23942397;