Genetic Variant NM_020345.4:c.-140+346T>C (chr3-23916438-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020345.4(NKIRAS1):c.-140+346T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,174 control chromosomes in the GnomAD database, including 10,741 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10739 hom., cov: 33)

Exomes 𝑓: 0.36 ( 2 hom. )

Consequence

NKIRAS1
NM_020345.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.881

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:

RPL15 (HGNC:10306): (ribosomal protein L15) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L15E family of ribosomal proteins and a component of the 60S subunit. This gene shares sequence similarity with the yeast ribosomal protein YL10 gene. Elevated expression of this gene has been observed in esophageal tumors and gastric cancer tissues, and deletion of this gene has been observed in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

RPL15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKIRAS1	NM_020345.4 link	c.-140+346T>C		intron_variant	Intron 1 of 4	ENST00000425478.7	NP_065078.1	Q9NYS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKIRAS1	ENST00000425478.7 link	c.-140+346T>C		intron_variant	Intron 1 of 4	1	NM_020345.4	ENSP00000400385.2		Q9NYS0

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55568

AN:

152020

Hom.:

10722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.361

AC:

AN:

Hom.:

Cov.:

AF XY:

0.367

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.366

AC:

55610

AN:

152138

Hom.:

10739

Cov.:

AF XY:

0.364

AC XY:

27051

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.423

Hom.:

18313

Bravo

AF:

0.368

Asia WGS

AF:

0.399

AC:

1390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.8

DANN

Benign

0.66

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over