rs41299193

chr14-50756742-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_020921.4(NIN):c.4288A>T(p.Ile1430Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,551,684 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1430T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (6 hom.)
• Consequence: NIN NM_020921.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.490

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004059702).
• BP6: Variant 14-50756742-T-A is Benign according to our data. Variant chr14-50756742-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 211613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIN	NM_020921.4	c.4288A>T	p.Ile1430Leu	missense_variant	18/31	ENST00000530997.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIN	ENST00000530997.7	c.4288A>T	p.Ile1430Leu	missense_variant	18/31	5	NM_020921.4	P2

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00196 AC: 303 AN: 154624 Hom.: 1 AF XY: 0.00218 AC XY: 177 AN XY: 81290

Gnomad AFR exome AF: 0.000905

Gnomad AMR exome AF: 0.000403

Gnomad ASJ exome AF: 0.000468

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00224

Gnomad FIN exome AF: 0.000784

Gnomad NFE exome AF: 0.00360

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.00351 AC: 4917 AN: 1399326 Hom.: 6 Cov.: 30 AF XY: 0.00356 AC XY: 2456 AN XY: 690178

Gnomad4 AFR exome AF: 0.000696

Gnomad4 AMR exome AF: 0.000560

Gnomad4 ASJ exome AF: 0.000596

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00218

Gnomad4 FIN exome AF: 0.00114

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152358 Hom.: 0 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74504

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00344 Hom.: 1

Bravo AF: 0.00198

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.00105 AC: 4

ESP6500EA AF: 0.00268 AC: 19

ExAC AF: 0.00152 AC: 67

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	NIN: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 18, 2015

- -

NIN-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.0020
Dann	Benign	0.21
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T;.;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.0041	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.76	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.19
MutPred		0.22		Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);Gain of catalytic residue at E1433 (P = 0.0669);
MVP		0.081
MPC		0.12
ClinPred		0.0018	T
GERP RS		-11
Varity_R		0.024
gMVP		0.11

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: rs41299193; hg19: chr14-51223460;