1-163344129-G-C

Variant names:

• chr1-163344129-G-C
• rs3013512
• NM_145697.3:c.807+259G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145697.3(NUF2):​c.807+259G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,118 control chromosomes in the GnomAD database, including 61,599 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 0.89 (61599 hom., cov: 32)
• Consequence: NUF2 NM_145697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUF2	NM_145697.3	c.807+259G>C		intron_variant	Intron 10 of 13	ENST00000271452.8	NP_663735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUF2	ENST00000271452.8	c.807+259G>C		intron_variant	Intron 10 of 13	1	NM_145697.3	ENSP00000271452.3

Frequencies

GnomAD3 genomes AF: 0.895 AC: 135983 AN: 152002 Hom.: 61580 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.913

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

GnomAD4 genome AF: 0.894 AC: 136052 AN: 152118 Hom.: 61599 Cov.: 32 AF XY: 0.896 AC XY: 66653 AN XY: 74358

African (AFR) AF: 0.732 AC: 30363 AN: 41462

American (AMR) AF: 0.912 AC: 13939 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3387 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5068 AN: 5182

South Asian (SAS) AF: 0.968 AC: 4664 AN: 4818

European-Finnish (FIN) AF: 0.971 AC: 10268 AN: 10578

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.961 AC: 65319 AN: 68000

Other (OTH) AF: 0.909 AC: 1922 AN: 2114

Alfa AF: 0.927 Hom.: 3196

Bravo AF: 0.884

Asia WGS AF: 0.923 AC: 3193 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.018
DANN	Benign	0.38
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3013512; hg19: chr1-163313919;