dbSNP rs61741547: NIN:p.Leu1730Val (chr14-50743529-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020921.4(NIN):c.5188T>G(p.Leu1730Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1730L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NIN
NM_020921.4 missense, splice_region

Scores

Splicing: ADA: 0.0001048

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

0 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:

LOC124903313 (HGNC:):

LOC124903313 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14577773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4 link	c.5188T>G	p.Leu1730Val	missense_variant, splice_region_variant	Exon 24 of 31	ENST00000530997.7	NP_065972.4	Q8N4C6-7Q5XUU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7 link	c.5188T>G	p.Leu1730Val	missense_variant, splice_region_variant	Exon 24 of 31	5	NM_020921.4	ENSP00000436092.2		Q8N4C6-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105378

Other (OTH)

AF:

0.00

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.031

.;.;.;.;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.82

T;.;.;T;T;T

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.84

L;L;.;.;L;.

PhyloP100

0.53

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.55

N;.;N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.39

T;.;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

1.0

D;D;.;.;D;B

Vest4

0.13

MutPred

0.11

Gain of methylation at K1729 (P = 0.0486);Gain of methylation at K1729 (P = 0.0486);.;.;Gain of methylation at K1729 (P = 0.0486);Gain of methylation at K1729 (P = 0.0486);

MVP

0.60

MPC

0.14

ClinPred

0.057

GERP RS

-3.5

Varity_R

0.036

gMVP

0.029

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.064

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over