chr14-50792726-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020921.4(NIN):​c.421G>A​(p.Gly141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

NIN
NM_020921.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.554
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0049036145).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NINNM_020921.4 linkuse as main transcriptc.421G>A p.Gly141Ser missense_variant 5/31 ENST00000530997.7 NP_065972.4 Q8N4C6-7Q5XUU0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NINENST00000530997.7 linkuse as main transcriptc.421G>A p.Gly141Ser missense_variant 5/315 NM_020921.4 ENSP00000436092.2 Q8N4C6-7

Frequencies

GnomAD3 genomes
AF:
0.000500
AC:
76
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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
GnomAD3 exomes
AF:
0.0000995
AC:
25
AN:
251312
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.00141
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000472
AC:
69
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00134
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000499
AC:
76
AN:
152262
Hom.:
0
Cov.:
32
AF XY:
0.000443
AC XY:
33
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00181
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000774
Hom.:
0
Bravo
AF:
0.000555
ESP6500AA
AF:
0.00250
AC:
11
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000157
AC:
19
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 22, 2015- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 27, 2023This variant is present in population databases (rs143800977, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 141 of the NIN protein (p.Gly141Ser). This variant has not been reported in the literature in individuals affected with NIN-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 211612). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
3.4
DANN
Benign
0.86
DEOGEN2
Benign
0.016
.;.;.;.;T;T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.57
T;.;.;T;T;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.0049
T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.46
N;N;N;N;N;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
1.4
N;.;N;N;N;N;N
REVEL
Benign
0.020
Sift
Benign
1.0
T;.;T;T;T;T;T
Sift4G
Benign
0.77
T;T;T;T;T;T;.
Polyphen
0.0020
B;B;.;.;B;B;.
Vest4
0.11
MVP
0.14
MPC
0.12
ClinPred
0.0069
T
GERP RS
-0.28
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.029
gMVP
0.38

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.

Other links and lift over

dbSNP: rs143800977; hg19: chr14-51259444; COSMIC: COSV99811279; COSMIC: COSV99811279; API