12-2830804-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031474.3(NRIP2):​c.399G>T​(p.Gln133His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NRIP2
NM_031474.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.395
Variant links:
Genes affected
NRIP2 (HGNC:23078): (nuclear receptor interacting protein 2) Predicted to enable aspartic-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within Notch signaling pathway and negative regulation of transcription by RNA polymerase II. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
ITFG2 (HGNC:30879): (integrin alpha FG-GAP repeat containing 2) Involved in cellular response to amino acid starvation; cellular response to glucose starvation; and negative regulation of TORC1 signaling. Located in lysosomal membrane. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.113102764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRIP2NM_031474.3 linkc.399G>T p.Gln133His missense_variant Exon 2 of 6 ENST00000337508.9 NP_113662.1 Q9BQI9-1
ITFG2NR_130744.3 linkn.2160C>A non_coding_transcript_exon_variant Exon 13 of 14
ITFG2NR_147202.2 linkn.1475-30C>A intron_variant Intron 12 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRIP2ENST00000337508.9 linkc.399G>T p.Gln133His missense_variant Exon 2 of 6 1 NM_031474.3 ENSP00000337501.4 Q9BQI9-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461600
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727106
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
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:
0.00000809
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.399G>T (p.Q133H) alteration is located in exon 2 (coding exon 2) of the NRIP2 gene. This alteration results from a G to T substitution at nucleotide position 399, causing the glutamine (Q) at amino acid position 133 to be replaced by a histidine (H). 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
0.15
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.052
T;T;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.44
T;T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.082
Sift
Uncertain
0.021
D;D;T
Sift4G
Benign
0.074
T;.;D
Polyphen
0.95
P;.;.
Vest4
0.39
MutPred
0.23
Gain of helix (P = 0.132);.;.;
MVP
0.16
MPC
0.15
ClinPred
0.53
D
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.077
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs1036210657; hg19: chr12-2939970; API