1-184795336-G-A

Position:

• chr1-184795336-G-A

Variant summary

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

The NM_052966.4(NIBAN1):​c.2428C>T​(p.Pro810Ser) 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. 15/21 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: NIBAN1 NM_052966.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.458

Genes affected

NIBAN1 (HGNC:16784): (niban apoptosis regulator 1) This gene encodes a member of the family with sequence similarity 129 protein family. This gene is highly expressed in several cancer cells and may serve as a prognostic marker for certain cancers. The encoded protein may play a role in regulating p53-mediated apoptosis. [provided by RefSeq, Sep 2016]

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=0.063038826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIBAN1	NM_052966.4	c.2428C>T	p.Pro810Ser	missense_variant	14/14	ENST00000367511.4	NP_443198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIBAN1	ENST00000367511.4	c.2428C>T	p.Pro810Ser	missense_variant	14/14	1	NM_052966.4	ENSP00000356481	P1
NIBAN1	ENST00000417056.5	c.260+2743C>T		intron_variant		3		ENSP00000414039
NIBAN1	ENST00000487074.5	n.1900C>T		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Dec 13, 2022

The c.2428C>T (p.P810S) alteration is located in exon 14 (coding exon 14) of the FAM129A gene. This alteration results from a C to T substitution at nucleotide position 2428, causing the proline (P) at amino acid position 810 to be replaced by a serine (S). 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	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.0070
Sift	Uncertain	0.021	D
Sift4G	Benign	0.25	T
Polyphen		0.077	B
Vest4		0.047
MutPred		0.29		Gain of phosphorylation at P810 (P = 0.0188);
MVP		0.11
MPC		0.093
ClinPred		0.046	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.19

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: chr1-184764470; COSMIC: COSV62283205;