chr1-163355453-T-G

Position:

• chr1-163355453-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145697.3(NUF2):​c.1379T>G​(p.Phe460Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: NUF2 NM_145697.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.094730794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUF2	NM_145697.3	c.1379T>G	p.Phe460Cys	missense_variant	14/14	ENST00000271452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUF2	ENST00000271452.8	c.1379T>G	p.Phe460Cys	missense_variant	14/14	1	NM_145697.3	P1
NUF2	ENST00000367900.7	c.1379T>G	p.Phe460Cys	missense_variant	14/14	1		P1
NUF2	ENST00000524800.5	c.1238T>G	p.Phe413Cys	missense_variant	13/13	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.91
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.55	T;.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.040	N;N;N
REVEL	Benign	0.027
Sift	Uncertain	0.027	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.0	B;B;B
Vest4		0.22
MutPred		0.13		.;Gain of methylation at K461 (P = 0.0248);Gain of methylation at K461 (P = 0.0248);
MVP		0.28
MPC		0.52
ClinPred		0.12	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.068
gMVP		0.20

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: rs933948175; hg19: chr1-163325243;