Variant chr3-23901022-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020345.4(NKIRAS1):c.122A>G(p.Asp41Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NKIRAS1
NM_020345.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKIRAS1	NM_020345.4 linkuse as main transcript	c.122A>G	p.Asp41Gly	missense_variant	4/5	ENST00000425478.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKIRAS1	ENST00000425478.7 linkuse as main transcript	c.122A>G	p.Asp41Gly	missense_variant	4/5	1	NM_020345.4	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727168

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:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 10, 2023

The c.122A>G (p.D41G) 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 122, causing the aspartic acid (D) at amino acid position 41 to be replaced by a glycine (G). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

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

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.90

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.89

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

MetaSVM

Uncertain

0.75

MutationAssessor

Pathogenic

4.0

H;H;H;H;H;.;.;.;H

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.6

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

REVEL

Pathogenic

0.93

Sift

Uncertain

0.0020

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

Sift4G

Benign

0.072

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

Polyphen

0.97

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

Vest4

0.75

MutPred

0.63

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

0.92

MPC

1.4

ClinPred

1.0

GERP RS

5.6

Varity_R

0.85

gMVP

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over