Variant chr14-50726007-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020921.4(NIN):c.6138A>T(p.Lys2046Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NIN
NM_020921.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.277

Variant links:

Genes affected

NIN (HGNC:14906): (ninein) This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

NIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.111124694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIN	NM_020921.4 linkuse as main transcript	c.6138A>T	p.Lys2046Asn	missense_variant	30/31	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7 linkuse as main transcript	c.6138A>T	p.Lys2046Asn	missense_variant	30/31	5	NM_020921.4	ENSP00000436092	P2	Q8N4C6-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251352

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.6138A>T (p.K2046N) alteration is located in exon 30 (coding exon 28) of the NIN gene. This alteration results from a A to T substitution at nucleotide position 6138, causing the lysine (K) at amino acid position 2046 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

.;.;.;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;.;.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

L;L;.;.;L

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.0

N;.;N;.;N

REVEL

Benign

0.020

Sift

Benign

0.21

T;.;T;.;T

Sift4G

Benign

0.074

T;T;T;T;D

Polyphen

0.058

B;B;.;.;B

Vest4

0.53

MutPred

0.22

Loss of ubiquitination at K2046 (P = 0.0141);Loss of ubiquitination at K2046 (P = 0.0141);.;.;Loss of ubiquitination at K2046 (P = 0.0141);

MVP

0.36

MPC

0.62

ClinPred

0.20

GERP RS

-1.1

Varity_R

0.083

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over