dbSNP rs187464517: NIN:p.Gln1222Arg (chr14-50757365-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_020921.4(NIN):c.3665A>G(p.Gln1222Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,613,990 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

NIN
NM_020921.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 0.784

Publications

4 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054405928).

BP6

Variant 14-50757365-T-C is Benign according to our data. Variant chr14-50757365-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 37290.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4 link	c.3665A>G	p.Gln1222Arg	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.3665A>G	p.Gln1222Arg	missense_variant	Exon 18 of 31	5	NM_020921.4	ENSP00000436092.2		Q8N4C6-7

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000697

AC:

175

AN:

251030

AF XY:

0.000575

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00507

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.000139

AC:

203

AN:

1461686

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33422

American (AMR)

AF:

0.00441

AC:

197

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111974

Other (OTH)

AF:

0.0000497

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000118

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41562

American (AMR)

AF:

0.00105

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

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:

0.0000908

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000511

AC:

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Seckel syndrome 7

Pathogenic:1

Nov 01, 2012

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

.;.;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.75

T;.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L;.

PhyloP100

0.78

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.8

N;.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.028

D;.;D;D

Sift4G

Benign

0.096

T;T;D;D

Polyphen

0.010

B;B;B;B

Vest4

0.34

MVP

0.26

MPC

0.14

ClinPred

0.036

GERP RS

3.5

Varity_R

0.13

gMVP

0.28

Mutation Taster

=93/7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over