Genetic Variant NIN:c.265+631A>G (chr14-50806106-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000530997.7(NIN):c.265+631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,312 control chromosomes in the GnomAD database, including 627 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 0.081 ( 627 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NIN
ENST00000530997.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.460

Publications

3 publications found

Variant links:

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)

NIN links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000530997.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NIN	NM_020921.4	MANE Select	c.265+631A>G	intron	N/A	NP_065972.4
NIN	NM_182946.2		c.265+631A>G	intron	N/A	NP_891991.2
NIN	NM_182944.3		c.265+631A>G	intron	N/A	NP_891989.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NIN	ENST00000530997.7	TSL:5 MANE Select	c.265+631A>G	intron	N/A	ENSP00000436092.2
NIN	ENST00000382041.7	TSL:1	c.265+631A>G	intron	N/A	ENSP00000371472.3
NIN	ENST00000382043.8	TSL:1	c.265+631A>G	intron	N/A	ENSP00000371474.4

Frequencies

GnomAD3 genomes

AF:

0.0806

AC:

12262

AN:

152194

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0925

Gnomad OTH

AF:

0.0913

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0805

AC:

12262

AN:

152312

Hom.:

627

Cov.:

AF XY:

0.0828

AC XY:

6163

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0198

AC:

823

AN:

41578

American (AMR)

AF:

0.133

AC:

2031

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

421

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

646

AN:

5184

South Asian (SAS)

AF:

0.101

AC:

488

AN:

4828

European-Finnish (FIN)

AF:

0.118

AC:

1251

AN:

10600

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0925

AC:

6292

AN:

68032

Other (OTH)

AF:

0.0932

AC:

197

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

582

1164

1745

2327

2909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0775

Hom.:

Bravo

AF:

0.0791

Asia WGS

AF:

0.109

AC:

378

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.0

(source)

DANN

Benign

0.81

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over