Variant chr20-25461554-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_025176.6(NINL):c.3664C>G(p.Leu1222Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,601,872 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

NINL
NM_025176.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0190

Variant links:

Genes affected

NINL (HGNC:29163): (ninein like) Predicted to enable calcium ion binding activity. Predicted to be involved in microtubule anchoring at centrosome. Located in cytosol; intercellular bridge; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

NINL links:

NINL (HGNC:):

NINL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004098356).

BP6

Variant 20-25461554-G-C is Benign according to our data. Variant chr20-25461554-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034254.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NINL	NM_025176.6 linkuse as main transcript	c.3664C>G	p.Leu1222Val	missense_variant	21/24	ENST00000278886.11	NP_079452.3	Q9Y2I6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NINL	ENST00000278886.11 linkuse as main transcript	c.3664C>G	p.Leu1222Val	missense_variant	21/24	1	NM_025176.6	ENSP00000278886.6		Q9Y2I6-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00234

AC:

563

AN:

240320

Hom.:

AF XY:

0.00236

AC XY:

306

AN XY:

129748

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.0000614

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00603

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00197

AC:

2862

AN:

1449570

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1368

AN XY:

720664

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00598

Gnomad4 NFE exome

AF:

0.00221

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152302

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00613

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00300

AC:

364

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NINL-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 27, 2020

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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.039

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.10

T;T

Polyphen

1.0

D;P

Vest4

0.10

MVP

0.24

MPC

0.13

ClinPred

0.012

GERP RS

2.0

Varity_R

0.13

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over