NM_020921.4:c.2987C>T

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.2987C>T(p.Ala996Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,614,162 control chromosomes in the GnomAD database, including 17 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. A996G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 17 hom. )

Consequence

NIN
NM_020921.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0110

Publications

8 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=0.0023878217).

BP6

Variant 14-50758043-G-A is Benign according to our data. Variant chr14-50758043-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 211604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020921.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIN	NM_020921.4	MANE Select	c.2987C>T	p.Ala996Val	missense	Exon 18 of 31	NP_065972.4
NIN	NM_182946.2		c.2987C>T	p.Ala996Val	missense	Exon 18 of 30	NP_891991.2	Q8N4C6-1
NIN	NM_182944.3		c.2987C>T	p.Ala996Val	missense	Exon 18 of 30	NP_891989.3	C9J066

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIN	ENST00000530997.7	TSL:5 MANE Select	c.2987C>T	p.Ala996Val	missense	Exon 18 of 31	ENSP00000436092.2	Q8N4C6-7
NIN	ENST00000382041.7	TSL:1	c.2987C>T	p.Ala996Val	missense	Exon 18 of 30	ENSP00000371472.3	Q8N4C6-1
NIN	ENST00000382043.8	TSL:1	c.2399+1814C>T		intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00391

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00224

AC:

563

AN:

251448

AF XY:

0.00227

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00389

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00396

AC:

5795

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

2820

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00190

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000603

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000768

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00480

AC:

5336

AN:

1112008

Other (OTH)

AF:

0.00416

AC:

251

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

321

641

962

1282

1603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

204

408

612

816

1020

<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:

0.00237

AC:

361

AN:

152276

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41564

American (AMR)

AF:

0.00248

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00391

AC:

266

AN:

68018

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00323

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00215

AC:

261

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00486

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

NIN-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.070

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.025

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.77

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.28

PhyloP100

-0.011

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.55

REVEL

Benign

0.045

Sift

Benign

1.0

Sift4G

Benign

0.30

Polyphen

0.015

Vest4

0.032

MVP

0.14

MPC

0.12

ClinPred

0.0040

GERP RS

-11

Varity_R

0.017

gMVP

0.016

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over