chr9-127507414-C-G

Variant summary

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

The NM_022833.4(NIBAN2):ā€‹c.1672G>Cā€‹(p.Val558Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000529 in 1,512,270 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000029 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27
Variant links:
Genes affected
NIBAN2 (HGNC:25282): (niban apoptosis regulator 2) Enables transcription coactivator activity. Involved in several processes, including gonadotropin secretion; positive regulation of transcription regulatory region DNA binding activity; and regulation of cellular macromolecule biosynthetic process. Located in several cellular components, including adherens junction; cytosol; and nucleoplasm. [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=0.21035501).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NIBAN2NM_022833.4 linkuse as main transcriptc.1672G>C p.Val558Leu missense_variant 14/14 ENST00000373312.4
NIBAN2NM_001035534.3 linkuse as main transcriptc.1633G>C p.Val545Leu missense_variant 14/14
NIBAN2XM_005252135.3 linkuse as main transcriptc.1891G>C p.Val631Leu missense_variant 15/15
NIBAN2XM_011518925.2 linkuse as main transcriptc.1762G>C p.Val588Leu missense_variant 15/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NIBAN2ENST00000373312.4 linkuse as main transcriptc.1672G>C p.Val558Leu missense_variant 14/141 NM_022833.4 P1Q96TA1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.00000614
AC:
1
AN:
162858
Hom.:
0
AF XY:
0.0000117
AC XY:
1
AN XY:
85602
show subpopulations
Gnomad AFR exome
AF:
0.0000698
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000294
AC:
4
AN:
1360072
Hom.:
0
Cov.:
31
AF XY:
0.00000451
AC XY:
3
AN XY:
665018
show subpopulations
Gnomad4 AFR exome
AF:
0.0000994
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:
0.00
Gnomad4 OTH exome
AF:
0.0000179
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
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:
0.0000302

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 submitterclinical testingAmbry GeneticsMar 01, 2024The c.1672G>C (p.V558L) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a G to C substitution at nucleotide position 1672, causing the valine (V) at amino acid position 558 to be replaced by a leucine (L). 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
0.33
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.9
.;M
MutationTaster
Benign
0.53
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.078
Sift
Benign
0.14
T;T
Sift4G
Uncertain
0.039
D;D
Polyphen
0.84
P;P
Vest4
0.11
MutPred
0.25
.;Loss of methylation at K554 (P = 0.072);
MVP
0.37
MPC
0.63
ClinPred
0.74
D
GERP RS
5.1
Varity_R
0.27
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.

Other links and lift over

dbSNP: rs999847409; hg19: chr9-130269693; API