Genetic Variant NIBAN3:p.Thr122Lys (chr19-17533639-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321827.2(NIBAN3):c.365C>A(p.Thr122Lys) 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 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T122M) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0880

Publications

0 publications found

Variant links:

Genes affected

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

NIBAN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1653795).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIBAN3	NM_001321827.2	MANE Select	c.365C>A	p.Thr122Lys	missense	Exon 4 of 15	NP_001308756.2	M0QXK3
NIBAN3	NM_173544.5		c.458C>A	p.Thr153Lys	missense	Exon 5 of 16	NP_775815.3
NIBAN3	NM_001321826.2		c.365C>A	p.Thr122Lys	missense	Exon 4 of 15	NP_001308755.2	M0R0E0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIBAN3	ENST00000599164.6	TSL:2 MANE Select	c.365C>A	p.Thr122Lys	missense	Exon 4 of 15	ENSP00000469225.1	M0QXK3
NIBAN3	ENST00000335393.8	TSL:1	c.458C>A	p.Thr153Lys	missense	Exon 5 of 16	ENSP00000335040.3	Q86XR2-1
NIBAN3	ENST00000595684.5	TSL:1	c.458C>A	p.Thr153Lys	missense	Exon 5 of 15	ENSP00000470106.1	Q86XR2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.00090

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.59

M_CAP

Benign

0.0051

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PhyloP100

0.088

PrimateAI

Benign

0.48

PROVEAN

Benign

2.3

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MutPred

0.62

Gain of ubiquitination at T153 (P = 0.0539)

MVP

0.13

MPC

0.12

ClinPred

0.68

GERP RS

3.0

Varity_R

0.052

gMVP

0.43

Mutation Taster

=85/15

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over