rs12893300

Variant names:

• chr14-50798735-C-T
• rs12893300
• NM_020921.4:c.266-5854G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020921.4(NIN):​c.266-5854G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,156 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (967 hom., cov: 32)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 4 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020921.4. 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.266-5854G>A		intron	N/A	NP_065972.4
	NIN	NM_182946.2		c.266-5854G>A		intron	N/A	NP_891991.2	Q8N4C6-1
	NIN	NM_182944.3		c.266-5854G>A		intron	N/A	NP_891989.3	C9J066

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.266-5854G>A		intron	N/A	ENSP00000436092.2	Q8N4C6-7
	NIN	ENST00000382041.7	TSL:1	c.266-5854G>A		intron	N/A	ENSP00000371472.3	Q8N4C6-1
	NIN	ENST00000382043.8	TSL:1	c.266-5854G>A		intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15461 AN: 152038 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15461 AN: 152156 Hom.: 967 Cov.: 32 AF XY: 0.104 AC XY: 7740 AN XY: 74362

African (AFR) AF: 0.0256 AC: 1062 AN: 41550

American (AMR) AF: 0.147 AC: 2244 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3464

East Asian (EAS) AF: 0.123 AC: 633 AN: 5158

South Asian (SAS) AF: 0.132 AC: 634 AN: 4806

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10570

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8474 AN: 68000

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.119 Hom.: 1884

Bravo AF: 0.0974

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.66
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: rs12893300; hg19: chr14-51265453; COSMIC: COSV55380802; COSMIC: COSV55380802;