9-127507135-T-C

Position:

• chr9-127507135-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022833.4(NIBAN2):​c.1951A>G​(p.Thr651Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NIBAN2 NM_022833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257

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 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=0.053177387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIBAN2	NM_022833.4	c.1951A>G	p.Thr651Ala	missense_variant	14/14	ENST00000373312.4
NIBAN2	NM_001035534.3	c.1912A>G	p.Thr638Ala	missense_variant	14/14
NIBAN2	XM_005252135.3	c.2170A>G	p.Thr724Ala	missense_variant	15/15
NIBAN2	XM_011518925.2	c.2041A>G	p.Thr681Ala	missense_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIBAN2	ENST00000373312.4	c.1951A>G	p.Thr651Ala	missense_variant	14/14	1	NM_022833.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 04, 2024

The c.1951A>G (p.T651A) alteration is located in exon 14 (coding exon 14) of the FAM129B gene. This alteration results from a A to G substitution at nucleotide position 1951, causing the threonine (T) at amino acid position 651 to be replaced by an alanine (A). 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	0.061
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	0.65	D;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.39	N;N
REVEL	Benign	0.049
Sift	Benign	0.35	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.015	B;B
Vest4		0.058
MutPred		0.14		.;Gain of helix (P = 0.0199);
MVP		0.15
MPC		0.27
ClinPred		0.080	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.22

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: chr9-130269414;