chr1-163345778-T-C

Position:

• chr1-163345778-T-C

Variant summary

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

The NM_145697.3(NUF2):​c.908T>C​(p.Leu303Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUF2 NM_145697.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.31

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUF2	NM_145697.3	c.908T>C	p.Leu303Pro	missense_variant	11/14	ENST00000271452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUF2	ENST00000271452.8	c.908T>C	p.Leu303Pro	missense_variant	11/14	1	NM_145697.3	P1
NUF2	ENST00000367900.7	c.908T>C	p.Leu303Pro	missense_variant	11/14	1		P1
NUF2	ENST00000524800.5	c.807+1908T>C		intron_variant		5
NUF2	ENST00000527439.5	n.478T>C		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

4p partial monosomy syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Service de Génétique Moléculaire, Hôpital Robert Debré

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.18	T;T
Polyphen		0.99	D;D
Vest4		0.80
MutPred		0.32		Gain of ubiquitination at K298 (P = 0.0357);Gain of ubiquitination at K298 (P = 0.0357);
MVP		0.63
MPC		1.3
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.70
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-163315568;