19-17530836-G-C

Variant names:

• chr19-17530836-G-C
• rs140895055
• NM_001321827.2:c.137G>C

Variant summary

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

The NM_001321827.2(NIBAN3):​c.137G>C​(p.Arg46Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NIBAN3 NM_001321827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.651

Genes affected

NIBAN3 (HGNC:24130): (niban apoptosis regulator 3)

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=0.22887051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIBAN3	NM_001321827.2	c.137G>C	p.Arg46Pro	missense_variant	Exon 2 of 15	ENST00000599164.6	NP_001308756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIBAN3	ENST00000599164.6	c.137G>C	p.Arg46Pro	missense_variant	Exon 2 of 15	2	NM_001321827.2	ENSP00000469225.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250450 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135434

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461412 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727032

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230G>C (p.R77P) alteration is located in exon 3 (coding exon 3) of the FAM129C gene. This alteration results from a G to C substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.2
DANN	Benign	0.93
DEOGEN2	Benign	0.0064	.;.;T;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.62	T;T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	.;N;N;.;.;.
REVEL	Benign	0.091
Sift	Benign	0.35	.;T;T;.;.;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		0.74	.;P;P;.;.;.
Vest4		0.63
MutPred		0.33		Loss of MoRF binding (P = 0.0141);Loss of MoRF binding (P = 0.0141);Loss of MoRF binding (P = 0.0141);.;.;.;
MVP		0.12
MPC		0.37
ClinPred		0.16	T
GERP RS		-2.0
Varity_R		0.25
gMVP		0.69

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: rs140895055; hg19: chr19-17641645;