19-17532323-C-G

Variant names:

• chr19-17532323-C-G
• rs758986033
• NM_001321827.2:c.247C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001321827.2(NIBAN3):​c.247C>G​(p.Arg83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NIBAN3 NM_001321827.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39851767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321827.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIBAN3	NM_001321827.2	MANE Select	c.247C>G	p.Arg83Gly	missense	Exon 3 of 15	NP_001308756.2	M0QXK3
	NIBAN3	NM_173544.5		c.340C>G	p.Arg114Gly	missense	Exon 4 of 16	NP_775815.3
	NIBAN3	NM_001321826.2		c.247C>G	p.Arg83Gly	missense	Exon 3 of 15	NP_001308755.2	M0R0E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIBAN3	ENST00000599164.6	TSL:2 MANE Select	c.247C>G	p.Arg83Gly	missense	Exon 3 of 15	ENSP00000469225.1	M0QXK3
	NIBAN3	ENST00000335393.8	TSL:1	c.340C>G	p.Arg114Gly	missense	Exon 4 of 16	ENSP00000335040.3	Q86XR2-1
	NIBAN3	ENST00000595684.5	TSL:1	c.340C>G	p.Arg114Gly	missense	Exon 4 of 15	ENSP00000470106.1	Q86XR2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250880 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.3
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.055
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.89	P
Vest4		0.31
MutPred		0.41		Loss of MoRF binding (P = 0.028)
MVP		0.17
MPC		0.22
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.29
gMVP		0.31
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs758986033; hg19: chr19-17643132;