chr3-23900972-G-A

Position:

• chr3-23900972-G-A

Variant summary

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

The NM_020345.4(NKIRAS1):​c.172C>T​(p.His58Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 4.49

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=0.40478894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKIRAS1	NM_020345.4	c.172C>T	p.His58Tyr	missense_variant	4/5	ENST00000425478.7	NP_065078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKIRAS1	ENST00000425478.7	c.172C>T	p.His58Tyr	missense_variant	4/5	1	NM_020345.4	ENSP00000400385.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.172C>T (p.H58Y) alteration is located in exon 4 (coding exon 2) of the NKIRAS1 gene. This alteration results from a C to T substitution at nucleotide position 172, causing the histidine (H) at amino acid position 58 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;T;T;T;T;T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.95	.;.;.;.;D;.;.;D;.
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.3	L;L;L;L;L;.;.;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N;N;N;N;.;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0060	D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D;D;D;D;D;D
Polyphen		0.59	P;P;P;P;P;B;B;B;P
Vest4		0.29
MutPred		0.54		Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);Gain of glycosylation at Y60 (P = 0.0317);
MVP		0.75
MPC		0.49
ClinPred		0.86	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.63

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: chr3-23942463;