rs769020357

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-17530787-C-T
• chr19-17530787-C-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>T​(p.Pro30Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NIBAN3 NM_001321827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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, 0.778

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>T	p.Pro30Ser	missense	Exon 2 of 15	NP_001308756.2	M0QXK3
	NIBAN3	NM_173544.5		c.181C>T	p.Pro61Ser	missense	Exon 3 of 16	NP_775815.3
	NIBAN3	NM_001321826.2		c.88C>T	p.Pro30Ser	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>T	p.Pro30Ser	missense	Exon 2 of 15	ENSP00000469225.1	M0QXK3
	NIBAN3	ENST00000335393.8	TSL:1	c.181C>T	p.Pro61Ser	missense	Exon 3 of 16	ENSP00000335040.3	Q86XR2-1
	NIBAN3	ENST00000595684.5	TSL:1	c.181C>T	p.Pro61Ser	missense	Exon 3 of 15	ENSP00000470106.1	Q86XR2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000799 AC: 2 AN: 250198 AF XY: 0.0000148

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460638 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726506

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111232

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.6
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.61		Loss of catalytic residue at P61 (P = 0.007)
MVP		0.46
MPC		0.42
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.39
gMVP		0.40
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;