9-127507930-T-A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.90

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.1591A>T	p.Ile531Phe	missense_variant	13/14	ENST00000373312.4
NIBAN2	NM_001035534.3	c.1552A>T	p.Ile518Phe	missense_variant	13/14
NIBAN2	XM_005252135.3	c.1810A>T	p.Ile604Phe	missense_variant	14/15
NIBAN2	XM_011518925.2	c.1681A>T	p.Ile561Phe	missense_variant	14/15

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727228

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.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

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	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	-0.0043
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.67	T
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	D
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

Other links and lift over

dbSNP: rs1588149264; hg19: chr9-130270209;