Genetic Variant NIBAN3:p.Arg4Trp (chr19-17527350-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001321827.2(NIBAN3):c.10C>T(p.Arg4Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,533,050 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 (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

NIBAN3
NM_001321827.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594

Variant links:

Genes affected

NIBAN3 (HGNC:24130): (niban apoptosis regulator 3)

NIBAN3 links:

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=0.056591272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIBAN3	NM_001321827.2 link	c.10C>T	p.Arg4Trp	missense_variant	Exon 1 of 15	ENST00000599164.6	NP_001308756.2	Q86XR2Q8N894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIBAN3	ENST00000599164.6 link	c.10C>T	p.Arg4Trp	missense_variant	Exon 1 of 15	2	NM_001321827.2	ENSP00000469225.1		M0QXK3

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

150736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000534

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000196

AC:

AN:

153208

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80852

show subpopulations

Gnomad AFR exome

AF:

0.000349

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:

0.0000239

AC:

AN:

1382190

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

681550

show subpopulations

Gnomad4 AFR exome

AF:

0.000547

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000865

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.000159

AC:

AN:

150860

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73720

show subpopulations

Gnomad4 AFR

AF:

0.000533

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000817

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000147

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103C>T (p.R35W) alteration is located in exon 2 (coding exon 2) of the FAM129C gene. This alteration results from a C to T substitution at nucleotide position 103, causing the arginine (R) at amino acid position 35 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

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0057

.;.;T;T;T;.;T

Eigen

Benign

-0.077

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.024

LIST_S2

Uncertain

0.86

D;D;D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.057

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;.;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

.;N;N;.;.;.;.

REVEL

Benign

0.047

Sift

Uncertain

0.017

.;D;D;.;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D

Polyphen

1.0

.;D;D;.;.;.;.

Vest4

0.35

MVP

0.24

MPC

0.42

ClinPred

0.39

GERP RS

3.1

Varity_R

0.068

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over