NM_001321827.2:c.178C>T

Variant summary

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

The NM_001321827.2(NIBAN3):​c.178C>T​(p.Arg60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000676 in 1,613,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

NIBAN3
NM_001321827.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.841
Variant links:
Genes affected
NIBAN3 (HGNC:24130): (niban apoptosis regulator 3)

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=0.06337726).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIBAN3NM_001321827.2 linkc.178C>T p.Arg60Cys missense_variant Exon 2 of 15 ENST00000599164.6 NP_001308756.2 Q86XR2Q8N894

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIBAN3ENST00000599164.6 linkc.178C>T p.Arg60Cys missense_variant Exon 2 of 15 2 NM_001321827.2 ENSP00000469225.1 M0QXK3

Frequencies

GnomAD3 genomes
AF:
0.000316
AC:
48
AN:
152130
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00111
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000478
GnomAD3 exomes
AF:
0.0000762
AC:
19
AN:
249474
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
134976
show subpopulations
Gnomad AFR exome
AF:
0.000865
Gnomad AMR exome
AF:
0.0000869
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:
0.00000887
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000411
AC:
60
AN:
1460768
Hom.:
0
Cov.:
31
AF XY:
0.0000372
AC XY:
27
AN XY:
726670
show subpopulations
Gnomad4 AFR exome
AF:
0.000897
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152248
Hom.:
0
Cov.:
31
AF XY:
0.000322
AC XY:
24
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00113
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:
0.000473
Alfa
AF:
0.0000594
Hom.:
0
Bravo
AF:
0.000400
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.271C>T (p.R91C) alteration is located in exon 3 (coding exon 3) of the FAM129C gene. This alteration results from a C to T substitution at nucleotide position 271, causing the arginine (R) at amino acid position 91 to be replaced by a cysteine (C). 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
0.099
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
.;.;T;T;T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.82
T;T;T;T;T;T
M_CAP
Benign
0.070
D
MetaRNN
Benign
0.063
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L;L;.;.;.
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-4.0
.;D;D;.;.;.
REVEL
Benign
0.068
Sift
Uncertain
0.0030
.;D;D;.;.;.
Sift4G
Uncertain
0.0080
D;D;D;D;D;D
Polyphen
1.0
.;D;D;.;.;.
Vest4
0.33
MVP
0.22
MPC
0.40
ClinPred
0.16
T
GERP RS
2.6
Varity_R
0.33
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs138634803; hg19: chr19-17641686; API