19-17530787-C-G

Variant names:

• chr19-17530787-C-G
• rs769020357
• NM_001321827.2:c.88C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001321827.2(NIBAN3):​c.88C>G​(p.Pro30Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P30S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: NIBAN3 NM_001321827.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

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.88C>G	p.Pro30Ala	missense	Exon 2 of 15	NP_001308756.2	M0QXK3
	NIBAN3	NM_173544.5		c.181C>G	p.Pro61Ala	missense	Exon 3 of 16	NP_775815.3
	NIBAN3	NM_001321826.2		c.88C>G	p.Pro30Ala	missense	Exon 2 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.88C>G	p.Pro30Ala	missense	Exon 2 of 15	ENSP00000469225.1	M0QXK3
	NIBAN3	ENST00000335393.8	TSL:1	c.181C>G	p.Pro61Ala	missense	Exon 3 of 16	ENSP00000335040.3	Q86XR2-1
	NIBAN3	ENST00000595684.5	TSL:1	c.181C>G	p.Pro61Ala	missense	Exon 3 of 15	ENSP00000470106.1	Q86XR2-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152240 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74438

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.6
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.28
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.62		Loss of catalytic residue at P61 (P = 0.0106)
MVP		0.46
MPC		0.41
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.34
gMVP		0.24
Mutation Taster		=84/16	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: rs769020357; hg19: chr19-17641596;