Genetic Variant NUF2:c.669+335G>A (chr1-163340761-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_145697.3(NUF2):c.669+335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,916 control chromosomes in the GnomAD database, including 26,574 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 0.59 ( 26574 hom., cov: 32)

Consequence

NUF2
NM_145697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

NUF2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_145697.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.97).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUF2	NM_145697.3	MANE Select	c.669+335G>A		intron	N/A	NP_663735.2	Q9BZD4
	NUF2	NM_031423.4		c.669+335G>A		intron	N/A	NP_113611.2	Q9BZD4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NUF2	ENST00000271452.8	TSL:1 MANE Select	c.669+335G>A	intron	N/A	ENSP00000271452.3	Q9BZD4
NUF2	ENST00000367900.7	TSL:1	c.669+335G>A	intron	N/A	ENSP00000356875.3	Q9BZD4
NUF2	ENST00000911840.1		c.669+335G>A	intron	N/A	ENSP00000581899.1

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89082

AN:

151798

Hom.:

26551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.712

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.637

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.587

AC:

89141

AN:

151916

Hom.:

26574

Cov.:

AF XY:

0.585

AC XY:

43468

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.503

AC:

20834

AN:

41404

American (AMR)

AF:

0.576

AC:

8794

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2478

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1921

AN:

5150

South Asian (SAS)

AF:

0.686

AC:

3306

AN:

4820

European-Finnish (FIN)

AF:

0.602

AC:

6336

AN:

10522

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.637

AC:

43283

AN:

67958

Other (OTH)

AF:

0.634

AC:

1340

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1870

3740

5610

7480

9350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.611

Hom.:

3708

Bravo

AF:

0.577

Asia WGS

AF:

0.548

AC:

1895

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.6

(source)

DANN

Benign

0.33

PhyloP100

-0.13

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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