rs2073348

chr14-50757940-T-Achr14-50757940-T-Cchr14-50757940-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.919

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]

ACMG classification

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	UniProt
NIN	NM_020921.4	c.3090A>T	p.Ser1030=	synonymous_variant	18/31	ENST00000530997.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIN	ENST00000530997.7	c.3090A>T	p.Ser1030=	synonymous_variant	18/31	5	NM_020921.4	P2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44258 AN: 151960 Hom.: 7003 Cov.: 32

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

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

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

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic 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

Other links and lift over

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