1-184795687-C-G

Position:

• chr1-184795687-C-G

Variant summary

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

The NM_052966.4(NIBAN1):​c.2077G>C​(p.Glu693Gln) 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: 32)
• Consequence: NIBAN1 NM_052966.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132

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=0.06328359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIBAN1	NM_052966.4	c.2077G>C	p.Glu693Gln	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.2077G>C	p.Glu693Gln	missense_variant	14/14	1	NM_052966.4	ENSP00000356481	P1
NIBAN1	ENST00000417056.5	c.260+2392G>C		intron_variant		3		ENSP00000414039
NIBAN1	ENST00000487074.5	n.1549G>C		non_coding_transcript_exon_variant	9/9	5

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

Nov 03, 2022

The c.2077G>C (p.E693Q) alteration is located in exon 14 (coding exon 14) of the FAM129A gene. This alteration results from a G to C substitution at nucleotide position 2077, causing the glutamic acid (E) at amino acid position 693 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	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.51
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.012
Sift	Benign	0.13	T
Sift4G	Benign	0.25	T
Polyphen		0.0040	B
Vest4		0.042
MutPred		0.14		Loss of loop (P = 0.1242);
MVP		0.20
MPC		0.079
ClinPred		0.050	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.10

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: chr1-184764821;