Genetic Variant NM_001321827.2:c.178C>T (chr19-17530877-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.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

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)

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=0.06337726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIBAN3	NM_001321827.2 link	c.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
NIBAN3	ENST00000599164.6 link	c.178C>T	p.Arg60Cys	missense_variant	Exon 2 of 15	2	NM_001321827.2	ENSP00000469225.1		M0QXK3

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152130

Hom.:

Cov.:

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:

AN:

249474

Hom.:

AF XY:

0.0000296

AC XY:

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:

AN:

1460768

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

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:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

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.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000289

AC:

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

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

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

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.063

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;.;.;.

PrimateAI

Benign

0.32

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

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.

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