ENST00000335393.8:c.13C>T

Variant names:

• chr19-17523451-C-T
• rs754299971
• ENST00000335393.8:c.13C>T

Variant summary

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

The ENST00000335393.8(NIBAN3):​c.13C>T​(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000556 in 1,563,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R5Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: NIBAN3 ENST00000335393.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.14
• Publications: 0 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=0.04667878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335393.8. 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_173544.5		c.13C>T	p.Arg5Trp	missense	Exon 1 of 16	NP_775815.3
	NIBAN3	NM_001098524.2		c.13C>T	p.Arg5Trp	missense	Exon 1 of 16	NP_001091994.2	Q86XR2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIBAN3	ENST00000335393.8	TSL:1	c.13C>T	p.Arg5Trp	missense	Exon 1 of 16	ENSP00000335040.3	Q86XR2-1
	NIBAN3	ENST00000595684.5	TSL:1	c.13C>T	p.Arg5Trp	missense	Exon 1 of 15	ENSP00000470106.1	Q86XR2-2
	NIBAN3	ENST00000332386.9	TSL:1	c.13C>T	p.Arg5Trp	missense	Exon 1 of 16	ENSP00000333447.4	Q86XR2-3

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000522 AC: 9 AN: 172460 AF XY: 0.0000658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000225

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000422

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000510 AC: 72 AN: 1411754 Hom.: 0 Cov.: 29 AF XY: 0.0000516 AC XY: 36 AN XY: 697254

African (AFR) AF: 0.0000305 AC: 1 AN: 32776

American (AMR) AF: 0.00 AC: 0 AN: 36004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25206

East Asian (EAS) AF: 0.0000797 AC: 3 AN: 37652

South Asian (SAS) AF: 0.000113 AC: 9 AN: 79996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000497 AC: 54 AN: 1085866

Other (OTH) AF: 0.0000854 AC: 5 AN: 58574

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41426

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000866 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000261 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.0
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.070
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.010	B
Vest4		0.12
MVP		0.061
MPC		0.33
ClinPred		0.10	T
GERP RS		-2.4
PromoterAI		-0.79	Under-expression
Varity_R		0.062
gMVP		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs754299971; hg19: chr19-17634260;