rs1022059

chr1-163340761-G-Achr1-163340761-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUF2	NM_145697.3	c.669+335G>A		intron_variant		ENST00000271452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUF2	ENST00000271452.8	c.669+335G>A		intron_variant		1	NM_145697.3	P1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89082 AN: 151798 Hom.: 26551 Cov.: 32

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.: 32 AF XY: 0.585 AC XY: 43468 AN XY: 74264

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.634

Alfa AF: 0.616 Hom.: 3610

Bravo AF: 0.577

Asia WGS AF: 0.548 AC: 1895 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.6
Dann	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1022059; hg19: chr1-163310551;