9-127507236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022833.4(NIBAN2):c.1850G>A(p.Arg617Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,458,786 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: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: NIBAN2 NM_022833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.370

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13789028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIBAN2	NM_022833.4	c.1850G>A	p.Arg617Gln	missense_variant	14/14	ENST00000373312.4
NIBAN2	NM_001035534.3	c.1811G>A	p.Arg604Gln	missense_variant	14/14
NIBAN2	XM_005252135.3	c.2069G>A	p.Arg690Gln	missense_variant	15/15
NIBAN2	XM_011518925.2	c.1940G>A	p.Arg647Gln	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4	c.1850G>A	p.Arg617Gln	missense_variant	14/14	1	NM_022833.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249210 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135216

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1458786 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

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

Sep 22, 2022

The c.1850G>A (p.R617Q) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a G to A substitution at nucleotide position 1850, causing the arginine (R) at amino acid position 617 to be replaced by a glutamine (Q). 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	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.87	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.055
Sift	Benign	0.070	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.91	P;P
Vest4		0.22
MutPred		0.19		.;Gain of ubiquitination at K615 (P = 0.0199);
MVP		0.34
MPC		0.60
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.061
gMVP		0.43

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: rs745760357; hg19: chr9-130269515; COSMIC: COSV55939983; COSMIC: COSV55939983;