14-50757940-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020921.4(NIN):​c.3090A>T​(p.Ser1030=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,906 control chromosomes in the GnomAD database, including 81,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7015 hom., cov: 32)
Exomes 𝑓: 0.31 ( 74001 hom. )

Consequence

NIN
NM_020921.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.919
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 Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 14-50757940-T-A is Benign according to our data. Variant chr14-50757940-T-A is described in ClinVar as [Benign]. Clinvar id is 129786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.919 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NINNM_020921.4 linkuse as main transcriptc.3090A>T p.Ser1030= synonymous_variant 18/31 ENST00000530997.7 NP_065972.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NINENST00000530997.7 linkuse as main transcriptc.3090A>T p.Ser1030= synonymous_variant 18/315 NM_020921.4 ENSP00000436092 P2Q8N4C6-7

Frequencies

GnomAD3 genomes
AF:
0.291
AC:
44258
AN:
151960
Hom.:
7003
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.194
Gnomad AMI
AF:
0.206
Gnomad AMR
AF:
0.405
Gnomad ASJ
AF:
0.355
Gnomad EAS
AF:
0.504
Gnomad SAS
AF:
0.241
Gnomad FIN
AF:
0.310
Gnomad MID
AF:
0.310
Gnomad NFE
AF:
0.307
Gnomad OTH
AF:
0.292
GnomAD3 exomes
AF:
0.336
AC:
84602
AN:
251454
Hom.:
15437
AF XY:
0.328
AC XY:
44618
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.189
Gnomad AMR exome
AF:
0.499
Gnomad ASJ exome
AF:
0.360
Gnomad EAS exome
AF:
0.510
Gnomad SAS exome
AF:
0.245
Gnomad FIN exome
AF:
0.309
Gnomad NFE exome
AF:
0.308
Gnomad OTH exome
AF:
0.324
GnomAD4 exome
AF:
0.314
AC:
458335
AN:
1461828
Hom.:
74001
Cov.:
50
AF XY:
0.310
AC XY:
225706
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.185
Gnomad4 AMR exome
AF:
0.485
Gnomad4 ASJ exome
AF:
0.358
Gnomad4 EAS exome
AF:
0.496
Gnomad4 SAS exome
AF:
0.244
Gnomad4 FIN exome
AF:
0.303
Gnomad4 NFE exome
AF:
0.309
Gnomad4 OTH exome
AF:
0.316
GnomAD4 genome
AF:
0.291
AC:
44283
AN:
152078
Hom.:
7015
Cov.:
32
AF XY:
0.295
AC XY:
21940
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.194
Gnomad4 AMR
AF:
0.406
Gnomad4 ASJ
AF:
0.355
Gnomad4 EAS
AF:
0.505
Gnomad4 SAS
AF:
0.241
Gnomad4 FIN
AF:
0.310
Gnomad4 NFE
AF:
0.307
Gnomad4 OTH
AF:
0.289
Alfa
AF:
0.269
Hom.:
1840
Bravo
AF:
0.299
Asia WGS
AF:
0.316
AC:
1100
AN:
3478
EpiCase
AF:
0.310
EpiControl
AF:
0.309

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.57
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs2073348; hg19: chr14-51224658; COSMIC: COSV55380503; API