Variant chr3-23901014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020345.4(NKIRAS1):c.130A>G(p.Met44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NKIRAS1
NM_020345.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Variant links:

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]

NKIRAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04608363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKIRAS1	NM_020345.4 link	c.130A>G	p.Met44Val	missense_variant	4/5	ENST00000425478.7	NP_065078.1	Q9NYS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKIRAS1	ENST00000425478.7 link	c.130A>G	p.Met44Val	missense_variant	4/5	1	NM_020345.4	ENSP00000400385.2		Q9NYS0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251156

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135786

show subpopulations

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

show subpopulations

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:

0.0000187

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 31, 2022

The c.130A>G (p.M44V) alteration is located in exon 4 (coding exon 2) of the NKIRAS1 gene. This alteration results from a A to G substitution at nucleotide position 130, causing the methionine (M) at amino acid position 44 to be replaced by a valine (V). 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

0.075

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.18

T;T;T;T;T;T;T;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.80

.;.;.;.;T;.;.;T;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.046

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.6

N;N;N;N;N;.;.;.;N

PrimateAI

Benign

0.39

PROVEAN

Benign

1.3

N;N;N;N;.;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;T;T;T;.;T;T;T;T

Sift4G

Benign

0.99

T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B;B;B;B

Vest4

0.056

MutPred

0.35

Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);Gain of glycosylation at Y43 (P = 0.0011);

MVP

0.56

MPC

0.41

ClinPred

0.051

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over