chr1-163326094-G-T

Position:

• chr1-163326094-G-T

Variant summary

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

The NM_145697.3(NUF2):​c.43G>T​(p.Val15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUF2 NM_145697.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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.43G>T	p.Val15Leu	missense_variant	2/14	ENST00000271452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUF2	ENST00000271452.8	c.43G>T	p.Val15Leu	missense_variant	2/14	1	NM_145697.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.43G>T (p.V15L) alteration is located in exon 2 (coding exon 1) of the NUF2 gene. This alteration results from a G to T substitution at nucleotide position 43, causing the valine (V) at amino acid position 15 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T;T;.;T;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.69	T;T;T;T;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;.;.;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Benign	0.096
Sift	Benign	0.036	D;D;D;D;D;D
Sift4G	Uncertain	0.038	D;D;D;D;D;D
Polyphen		0.0090, 0.0010, 0.023	.;.;B;B;B;B
Vest4		0.22, 0.21
MutPred		0.87		Loss of catalytic residue at V15 (P = 0.1865);Loss of catalytic residue at V15 (P = 0.1865);Loss of catalytic residue at V15 (P = 0.1865);Loss of catalytic residue at V15 (P = 0.1865);Loss of catalytic residue at V15 (P = 0.1865);Loss of catalytic residue at V15 (P = 0.1865);
MVP		0.67
MPC		0.36
ClinPred		0.34	T
GERP RS		1.4
Varity_R		0.35
gMVP		0.78

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: chr1-163295884;