Variant 9-127507008-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022833.4(NIBAN2):c.2078C>T(p.Pro693Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000084 in 1,594,296 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 (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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:

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=0.057654202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NIBAN2	NM_022833.4 linkuse as main transcript	c.2078C>T	p.Pro693Leu	missense_variant	14/14	ENST00000373312.4
NIBAN2	NM_001035534.3 linkuse as main transcript	c.2039C>T	p.Pro680Leu	missense_variant	14/14
NIBAN2	XM_005252135.3 linkuse as main transcript	c.2297C>T	p.Pro766Leu	missense_variant	15/15
NIBAN2	XM_011518925.2 linkuse as main transcript	c.2168C>T	p.Pro723Leu	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4 linkuse as main transcript	c.2078C>T	p.Pro693Leu	missense_variant	14/14	1	NM_022833.4	P1	Q96TA1-1
NIBAN2	ENST00000373314.7 linkuse as main transcript	c.2039C>T	p.Pro680Leu	missense_variant	14/14	1			Q96TA1-2
NIBAN2	ENST00000478917.1 linkuse as main transcript	n.211-1514C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

224540

Hom.:

AF XY:

0.0000652

AC XY:

AN XY:

122662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.000241

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000519

Gnomad NFE exome

AF:

0.0000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000839

AC:

121

AN:

1442074

Hom.:

Cov.:

AF XY:

0.0000797

AC XY:

AN XY:

715304

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000927

Gnomad4 ASJ exome

AF:

0.0000801

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000662

AC:

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

Nov 15, 2021

The c.2078C>T (p.P693L) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a C to T substitution at nucleotide position 2078, causing the proline (P) at amino acid position 693 to be replaced by a leucine (L). 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

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.047

.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.040

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.12

MPC

0.30

ClinPred

0.10

GERP RS

4.0

Varity_R

0.081

gMVP

0.31

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