Variant chr2-200893289-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001369441.2(NIF3L1):c.480C>G(p.Asn160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,590,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

NIF3L1
NM_001369441.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.375

Variant links:

Genes affected

NIF3L1 (HGNC:13390): (NGG1 interacting factor 3 like 1) Enables identical protein binding activity. Involved in positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NIF3L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035977095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIF3L1	NM_001369441.2 linkuse as main transcript	c.480C>G	p.Asn160Lys	missense_variant	3/7	ENST00000409020.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIF3L1	ENST00000409020.6 linkuse as main transcript	c.480C>G	p.Asn160Lys	missense_variant	3/7	5	NM_001369441.2	P1	Q9GZT8-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000216

AC:

AN:

235698

Hom.:

AF XY:

0.000218

AC XY:

AN XY:

128644

show subpopulations

Gnomad AFR exome

AF:

0.000351

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000417

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000524

AC:

753

AN:

1438252

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

356

AN XY:

714416

show subpopulations

Gnomad4 AFR exome

AF:

0.0000939

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000641

Gnomad4 OTH exome

AF:

0.000760

GnomAD4 genome

AF:

0.000434

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.000427

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000542

AC:

ESP6500EA

AF:

0.00110

AC:

ExAC

AF:

0.000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.480C>G (p.N160K) alteration is located in exon 3 (coding exon 2) of the NIF3L1 gene. This alteration results from a C to G substitution at nucleotide position 480, causing the asparagine (N) at amino acid position 160 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.037

.;.;T;.;T;T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

T;T;T;T;.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.036

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.0

N;N;N;N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.16

T;T;T;T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;T;T;T

Polyphen

0.0010

.;.;B;.;B;.;.;.

Vest4

0.10, 0.088, 0.14, 0.13

MutPred

0.54

.;Gain of ubiquitination at N160 (P = 0.0203);Gain of ubiquitination at N160 (P = 0.0203);.;Gain of ubiquitination at N160 (P = 0.0203);.;Gain of ubiquitination at N160 (P = 0.0203);Gain of ubiquitination at N160 (P = 0.0203);

MVP

0.27

MPC

0.050

ClinPred

0.018

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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