chr9-127507146-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022833.4(NIBAN2):​c.1940C>T​(p.Pro647Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,606,240 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05423373).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NIBAN2NM_022833.4 linkuse as main transcriptc.1940C>T p.Pro647Leu missense_variant 14/14 ENST00000373312.4 NP_073744.2
NIBAN2NM_001035534.3 linkuse as main transcriptc.1901C>T p.Pro634Leu missense_variant 14/14 NP_001030611.1
NIBAN2XM_005252135.3 linkuse as main transcriptc.2159C>T p.Pro720Leu missense_variant 15/15 XP_005252192.3
NIBAN2XM_011518925.2 linkuse as main transcriptc.2030C>T p.Pro677Leu missense_variant 15/15 XP_011517227.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NIBAN2ENST00000373312.4 linkuse as main transcriptc.1940C>T p.Pro647Leu missense_variant 14/141 NM_022833.4 ENSP00000362409 P1Q96TA1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000128
AC:
3
AN:
233710
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
127280
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000577
Gnomad SAS exome
AF:
0.0000340
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000961
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000186
AC:
27
AN:
1454004
Hom.:
0
Cov.:
31
AF XY:
0.0000152
AC XY:
11
AN XY:
722868
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000230
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.0000193
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
ExAC
AF:
0.0000247
AC:
3

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 GeneticsNov 23, 2021The c.1940C>T (p.P647L) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a C to T substitution at nucleotide position 1940, causing the proline (P) at amino acid position 647 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
0.071
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.061
.;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.5
D;D
REVEL
Benign
0.054
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.060
B;B
Vest4
0.043
MutPred
0.15
.;Loss of relative solvent accessibility (P = 0.0186);
MVP
0.17
MPC
0.28
ClinPred
0.88
D
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
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: rs552467244; hg19: chr9-130269425; API