Variant 1-163338056-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145697.3(NUF2):c.472G>A(p.Ala158Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00755 in 1,612,662 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 44 hom. )

Consequence

NUF2
NM_145697.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.64

Variant links:

Genes affected

NUF2 (HGNC:14621): (NUF2 component of NDC80 kinetochore complex) This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

NUF2 links:

NUF2 (HGNC:):

NUF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004669547).

BP6

Variant 1-163338056-G-A is Benign according to our data. Variant chr1-163338056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3387942.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUF2	NM_145697.3 linkuse as main transcript	c.472G>A	p.Ala158Thr	missense_variant	7/14	ENST00000271452.8	NP_663735.2	Q9BZD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUF2	ENST00000271452.8 linkuse as main transcript	c.472G>A	p.Ala158Thr	missense_variant	7/14	1	NM_145697.3	ENSP00000271452.3		Q9BZD4

Frequencies

GnomAD3 genomes

AF:

0.00682

AC:

1036

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00912

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00966

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00896

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.00661

AC:

1660

AN:

251178

Hom.:

AF XY:

0.00641

AC XY:

871

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.00845

Gnomad OTH exome

AF:

0.00865

GnomAD4 exome

AF:

0.00763

AC:

11146

AN:

1460750

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

5346

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00736

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.00948

Gnomad4 NFE exome

AF:

0.00827

Gnomad4 OTH exome

AF:

0.00890

GnomAD4 genome

AF:

0.00681

AC:

1035

AN:

151912

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

491

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00210

Gnomad4 AMR

AF:

0.00911

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00966

Gnomad4 NFE

AF:

0.00896

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00827

Hom.:

Bravo

AF:

0.00716

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00619

AC:

752

EpiCase

AF:

0.00890

EpiControl

AF:

0.00854

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

NUF2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.024

.;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.68

T;T;.;T

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.90

N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.11

B;B;B;B

Vest4

0.47

MVP

0.28

MPC

0.35

ClinPred

0.025

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.23

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