Variant 9-127507236-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022833.4(NIBAN2):c.1850G>A(p.Arg617Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,458,786 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: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370

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]

NIBAN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13789028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NIBAN2	NM_022833.4 linkuse as main transcript	c.1850G>A	p.Arg617Gln	missense_variant	14/14	ENST00000373312.4
NIBAN2	NM_001035534.3 linkuse as main transcript	c.1811G>A	p.Arg604Gln	missense_variant	14/14
NIBAN2	XM_005252135.3 linkuse as main transcript	c.2069G>A	p.Arg690Gln	missense_variant	15/15
NIBAN2	XM_011518925.2 linkuse as main transcript	c.1940G>A	p.Arg647Gln	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4 linkuse as main transcript	c.1850G>A	p.Arg617Gln	missense_variant	14/14	1	NM_022833.4	P1	Q96TA1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249210

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1458786

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Sep 22, 2022

The c.1850G>A (p.R617Q) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a G to A substitution at nucleotide position 1850, causing the arginine (R) at amino acid position 617 to be replaced by a glutamine (Q). 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

0.079

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;M

MutationTaster

Benign

0.87

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.055

Sift

Benign

0.070

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.91

P;P

Vest4

0.22

MutPred

0.19

.;Gain of ubiquitination at K615 (P = 0.0199);

MVP

0.34

MPC

0.60

ClinPred

0.83

GERP RS

4.3

Varity_R

0.061

gMVP

0.43

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.

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