chr9-127508149-G-C

Position:

• chr9-127508149-G-C

Variant summary

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

The NM_022833.4(NIBAN2):​c.1486C>G​(p.Leu496Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIBAN2 NM_022833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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]

ACMG classification

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	UniProt
NIBAN2	NM_022833.4	c.1486C>G	p.Leu496Val	missense_variant	12/14	ENST00000373312.4
NIBAN2	NM_001035534.3	c.1447C>G	p.Leu483Val	missense_variant	12/14
NIBAN2	XM_005252135.3	c.1705C>G	p.Leu569Val	missense_variant	13/15
NIBAN2	XM_011518925.2	c.1576C>G	p.Leu526Val	missense_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4	c.1486C>G	p.Leu496Val	missense_variant	12/14	1	NM_022833.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.1486C>G (p.L496V) alteration is located in exon 12 (coding exon 12) of the FAM129B gene. This alteration results from a C to G substitution at nucleotide position 1486, causing the leucine (L) at amino acid position 496 to be replaced by a valine (V). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.93	P;D
Vest4		0.47
MutPred		0.74		.;Gain of sheet (P = 0.0344);
MVP		0.37
MPC		0.48
ClinPred		0.93	D
GERP RS		2.8
Varity_R		0.75
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130270428;