14-50725941-G-A

Variant names:

• chr14-50725941-G-A
• rs1983764
• ENST00000382041.7:c.6204C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182946.2(NIN):​c.6204C>T​(p.Pro2068Pro) 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 NM_182946.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.970
• Publications: 31 publications found

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]

NIN Gene-Disease associations (from GenCC):

• Seckel syndrome 7

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP6: Variant 14-50725941-G-A is Benign according to our data. Variant chr14-50725941-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	NM_020921.4	MANE Select	c.6192+12C>T		intron	N/A	NP_065972.4
	NIN	NM_182946.2		c.6204C>T	p.Pro2068Pro	synonymous	Exon 30 of 30	NP_891991.2	Q8N4C6-1
	NIN	NM_016350.5		c.4065C>T	p.Pro1355Pro	synonymous	Exon 29 of 29	NP_057434.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000382041.7	TSL:1	c.6204C>T	p.Pro2068Pro	synonymous	Exon 30 of 30	ENSP00000371472.3	Q8N4C6-1
	NIN	ENST00000382043.8	TSL:1	c.4065C>T	p.Pro1355Pro	synonymous	Exon 28 of 28	ENSP00000371474.4	Q8N4C6-11
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.6192+12C>T		intron	N/A	ENSP00000436092.2	Q8N4C6-7

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

GnomAD2 exomes AF: 0.336 AC: 84340 AN: 251296 AF XY: 0.344

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 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

African (AFR) AF: 0.0699 AC: 2340 AN: 33474

American (AMR) AF: 0.279 AC: 12495 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8220 AN: 26128

East Asian (EAS) AF: 0.290 AC: 11511 AN: 39684

South Asian (SAS) AF: 0.380 AC: 32805 AN: 86230

European-Finnish (FIN) AF: 0.445 AC: 23769 AN: 53418

Middle Eastern (MID) AF: 0.319 AC: 1842 AN: 5766

European-Non Finnish (NFE) AF: 0.364 AC: 404525 AN: 1111608

Other (OTH) AF: 0.336 AC: 20295 AN: 60380

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

African (AFR) AF: 0.0822 AC: 3413 AN: 41500

American (AMR) AF: 0.257 AC: 3928 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3464

East Asian (EAS) AF: 0.313 AC: 1619 AN: 5168

South Asian (SAS) AF: 0.381 AC: 1831 AN: 4806

European-Finnish (FIN) AF: 0.430 AC: 4539 AN: 10546

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24861 AN: 67942

Other (OTH) AF: 0.291 AC: 614 AN: 2112

Alfa AF: 0.332 Hom.: 8143

Bravo AF: 0.258

Asia WGS AF: 0.345 AC: 1200 AN: 3474

EpiCase AF: 0.355

EpiControl AF: 0.355

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Seckel syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.31
DANN	Benign	0.36
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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