19-17523451-C-T

Variant summary

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

The NM_173544.5(NIBAN3):​c.13C>T​(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000556 in 1,563,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R5G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

NIBAN3
NM_173544.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.14
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=0.04667878).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIBAN3NM_173544.5 linkc.13C>T p.Arg5Trp missense_variant Exon 1 of 16 NP_775815.3 Q86XR2-1
NIBAN3NM_001098524.2 linkc.13C>T p.Arg5Trp missense_variant Exon 1 of 16 NP_001091994.2 Q86XR2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIBAN3ENST00000335393.8 linkc.13C>T p.Arg5Trp missense_variant Exon 1 of 16 1 ENSP00000335040.3 Q86XR2-1
NIBAN3ENST00000595684.5 linkc.13C>T p.Arg5Trp missense_variant Exon 1 of 15 1 ENSP00000470106.1 Q86XR2-2
NIBAN3ENST00000332386.9 linkc.13C>T p.Arg5Trp missense_variant Exon 1 of 16 1 ENSP00000333447.4 Q86XR2-3

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000522
AC:
9
AN:
172460
Hom.:
0
AF XY:
0.0000658
AC XY:
6
AN XY:
91176
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000225
Gnomad SAS exome
AF:
0.000127
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000422
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000510
AC:
72
AN:
1411754
Hom.:
0
Cov.:
29
AF XY:
0.0000516
AC XY:
36
AN XY:
697254
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000797
Gnomad4 SAS exome
AF:
0.000113
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000497
Gnomad4 OTH exome
AF:
0.0000854
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000866
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.0000261
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 28, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13C>T (p.R5W) alteration is located in exon 1 (coding exon 1) of the FAM129C gene. This alteration results from a C to T substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a tryptophan (W). 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
0.12
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
4.0
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0030
.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.63
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.75
.;N;N
REVEL
Benign
0.070
Sift
Uncertain
0.0060
.;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.010, 0.0030
.;B;B
Vest4
0.12
MVP
0.061
MPC
0.33
ClinPred
0.10
T
GERP RS
-2.4
Varity_R
0.062
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs754299971; hg19: chr19-17634260; API