NM_001321827.2:c.178C>T

Variant names:

• chr19-17530877-C-T
• rs138634803
• NM_001321827.2:c.178C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001321827.2(NIBAN3):​c.178C>T​(p.Arg60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000676 in 1,613,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R60H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: NIBAN3 NM_001321827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.841
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06337726).

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.178C>T	p.Arg60Cys	missense	Exon 2 of 15	NP_001308756.2	M0QXK3
	NIBAN3	NM_173544.5		c.271C>T	p.Arg91Cys	missense	Exon 3 of 16	NP_775815.3
	NIBAN3	NM_001321826.2		c.178C>T	p.Arg60Cys	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.178C>T	p.Arg60Cys	missense	Exon 2 of 15	ENSP00000469225.1	M0QXK3
	NIBAN3	ENST00000335393.8	TSL:1	c.271C>T	p.Arg91Cys	missense	Exon 3 of 16	ENSP00000335040.3	Q86XR2-1
	NIBAN3	ENST00000595684.5	TSL:1	c.271C>T	p.Arg91Cys	missense	Exon 3 of 15	ENSP00000470106.1	Q86XR2-2

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000762 AC: 19 AN: 249474 AF XY: 0.0000296

Gnomad AFR exome AF: 0.000865

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1460768 Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27 AN XY: 726670

African (AFR) AF: 0.000897 AC: 30 AN: 33440

American (AMR) AF: 0.0000447 AC: 2 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111706

Other (OTH) AF: 0.0000497 AC: 3 AN: 60366

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152248 Hom.: 0 Cov.: 31 AF XY: 0.000322 AC XY: 24 AN XY: 74436

African (AFR) AF: 0.00113 AC: 47 AN: 41538

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000310 Hom.: 0

Bravo AF: 0.000400

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.099
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.84
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.068
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.33
MVP		0.22
MPC		0.40
ClinPred		0.16	T
GERP RS		2.6
Varity_R		0.33
gMVP		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138634803; hg19: chr19-17641686;