Variant 9-127507930-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022833.4(NIBAN2):c.1591A>T(p.Ile531Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NIBAN2	NM_022833.4 linkuse as main transcript	c.1591A>T	p.Ile531Phe	missense_variant	13/14	ENST00000373312.4
NIBAN2	NM_001035534.3 linkuse as main transcript	c.1552A>T	p.Ile518Phe	missense_variant	13/14
NIBAN2	XM_005252135.3 linkuse as main transcript	c.1810A>T	p.Ile604Phe	missense_variant	14/15
NIBAN2	XM_011518925.2 linkuse as main transcript	c.1681A>T	p.Ile561Phe	missense_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4 linkuse as main transcript	c.1591A>T	p.Ile531Phe	missense_variant	13/14	1	NM_022833.4	P1	Q96TA1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

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

Jul 13, 2021

The c.1591A>T (p.I531F) alteration is located in exon 13 (coding exon 13) of the FAM129B gene. This alteration results from a A to T substitution at nucleotide position 1591, causing the isoleucine (I) at amino acid position 531 to be replaced by a phenylalanine (F). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

.;T

Eigen

Benign

-0.0043

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.82

P;P

Vest4

0.82

MutPred

0.46

.;Loss of sheet (P = 0.0817);

MVP

0.34

MPC

1.0

ClinPred

0.95

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.71

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