14-50725941-G-A

Variant summary

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

The ENST00000382041.7(NIN):c.6204C>T(p.Pro2068=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,613,432 control chromosomes in the GnomAD database, including 101,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7244 hom., cov: 31)
  • Exomes 𝑓: 0.35 (94288 hom.)
• Consequence: NIN ENST00000382041.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.970

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 14-50725941-G-A is Benign according to our data. Variant chr14-50725941-G-A is described in ClinVar as [Benign]. Clinvar id is 1250757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50725941-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIN	NM_020921.4	c.6192+12C>T		intron_variant		ENST00000530997.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIN	ENST00000530997.7	c.6192+12C>T		intron_variant		5	NM_020921.4	P2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42399 AN: 151906 Hom.: 7245 Cov.: 31

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.336 AC: 84340 AN: 251296 Hom.: 15257 AF XY: 0.344 AC XY: 46740 AN XY: 135808

Gnomad AFR exome AF: 0.0765

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.320

Gnomad SAS exome AF: 0.379

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.354 AC: 517802 AN: 1461408 Hom.: 94288 Cov.: 35 AF XY: 0.356 AC XY: 259079 AN XY: 727036

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.279 AC: 42390 AN: 152024 Hom.: 7244 Cov.: 31 AF XY: 0.281 AC XY: 20856 AN XY: 74288

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.291

Alfa AF: 0.331 Hom.: 7691

Bravo AF: 0.258

Asia WGS AF: 0.345 AC: 1200 AN: 3474

EpiCase AF: 0.355

EpiControl AF: 0.355

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	Aug 29, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Seckel syndrome 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.31
Dann	Benign	0.36

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: rs1983764; hg19: chr14-51192659; COSMIC: COSV55382445; COSMIC: COSV55382445;