Variant 9-127507248-G-A 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.1838C>T(p.Ser613Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,609,936 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

NIBAN2
NM_022833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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=0.07925081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NIBAN2	NM_022833.4 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	14/14	ENST00000373312.4	NP_073744.2
NIBAN2	NM_001035534.3 linkuse as main transcript	c.1799C>T	p.Ser600Leu	missense_variant	14/14		NP_001030611.1
NIBAN2	XM_005252135.3 linkuse as main transcript	c.2057C>T	p.Ser686Leu	missense_variant	15/15		XP_005252192.3
NIBAN2	XM_011518925.2 linkuse as main transcript	c.1928C>T	p.Ser643Leu	missense_variant	15/15		XP_011517227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIBAN2	ENST00000373312.4 linkuse as main transcript	c.1838C>T	p.Ser613Leu	missense_variant	14/14	1	NM_022833.4	ENSP00000362409	P1	Q96TA1-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000129

AC:

AN:

248396

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

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:

0.000197

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000102

AC:

148

AN:

1457796

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

724576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000380

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000723

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:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

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

May 17, 2023

The c.1838C>T (p.S613L) 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 1838, causing the serine (S) at amino acid position 613 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

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.079

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.075

T;T

Polyphen

0.32

B;B

Vest4

0.084

MVP

0.26

MPC

0.34

ClinPred

0.076

GERP RS

5.3

Varity_R

0.087

gMVP

0.24

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