chr14-50756742-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020921.4(NIN):c.4288A>T(p.Ile1430Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,551,684 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1430T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 6 hom. )

Consequence

NIN
NM_020921.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.490

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Seckel syndrome 7
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

NIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004059702).

BP6

Variant 14-50756742-T-A is Benign according to our data. Variant chr14-50756742-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 211613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4 link	c.4288A>T	p.Ile1430Leu	missense_variant	Exon 18 of 31	ENST00000530997.7	NP_065972.4	Q8N4C6-7Q5XUU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7 link	c.4288A>T	p.Ile1430Leu	missense_variant	Exon 18 of 31	5	NM_020921.4	ENSP00000436092.2		Q8N4C6-7

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00196

AC:

303

AN:

154624

AF XY:

0.00218

show subpopulations

Gnomad AFR exome

AF:

0.000905

Gnomad AMR exome

AF:

0.000403

Gnomad ASJ exome

AF:

0.000468

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000784

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.00351

AC:

4917

AN:

1399326

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2456

AN XY:

690178

show subpopulations

African (AFR)

AF:

0.000696

AC:

AN:

31598

American (AMR)

AF:

0.000560

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.000596

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00218

AC:

173

AN:

79244

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

49188

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00410

AC:

4425

AN:

1078974

Other (OTH)

AF:

0.00353

AC:

205

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

307

614

920

1227

1534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152358

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41584

American (AMR)

AF:

0.000849

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00365

AC:

248

AN:

68026

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00344

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00105

AC:

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.00152

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NIN: BP4, BS2 -

not specified

Benign:1

Sep 18, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NIN-related disorder

Benign:1

Feb 22, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.0020

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.020

.;.;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.58

T;.;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;N;N;.

PhyloP100

-0.49

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.76

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.19

MutPred

0.22

Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);

MVP

0.081

MPC

0.12

ClinPred

0.0018

GERP RS

-11

Varity_R

0.024

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over