Variant chr3-23893331-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

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 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=0.3571002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKIRAS1	NM_020345.4 linkuse as main transcript	c.343A>T	p.Ile115Phe	missense_variant	5/5	ENST00000425478.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKIRAS1	ENST00000425478.7 linkuse as main transcript	c.343A>T	p.Ile115Phe	missense_variant	5/5	1	NM_020345.4	P3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jun 23, 2023

The c.343A>T (p.I115F) alteration is located in exon 5 (coding exon 3) of the NKIRAS1 gene. This alteration results from a A to T substitution at nucleotide position 343, causing the isoleucine (I) at amino acid position 115 to be replaced by a phenylalanine (F). 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

0.32

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Uncertain

0.57

D;D;D;D;D;D;D;D;D

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.073

MetaRNN

Benign

0.35

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

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.8

L;L;L;L;L;.;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.9

D;D;D;D;.;D;D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.061

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

Sift4G

Uncertain

0.0080

D;D;D;D;D;D;D;D;D

Polyphen

0.19

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

Vest4

0.40

MutPred

0.66

Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);Gain of glycosylation at T114 (P = 0.082);

MVP

0.71

MPC

0.78

ClinPred

0.70

GERP RS

5.0

Varity_R

0.23

gMVP

0.75

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

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