Variant 18-2575030-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006101.3(NDC80):c.143C>T(p.Pro48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,611,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NDC80
NM_006101.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

NDC80 (HGNC:16909): (NDC80 kinetochore complex component) This gene encodes a component of the NDC80 kinetochore complex. The encoded protein consists of an N-terminal microtubule binding domain and a C-terminal coiled-coiled domain that interacts with other components of the complex. This protein functions to organize and stabilize microtubule-kinetochore interactions and is required for proper chromosome segregation. [provided by RefSeq, Oct 2011]

NDC80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1914781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDC80	NM_006101.3 linkuse as main transcript	c.143C>T	p.Pro48Leu	missense_variant	3/17	ENST00000261597.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDC80	ENST00000261597.9 linkuse as main transcript	c.143C>T	p.Pro48Leu	missense_variant	3/17	1	NM_006101.3	P1
NDC80	ENST00000575515.1 linkuse as main transcript	c.143C>T	p.Pro48Leu	missense_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249562

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134960

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459204

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.143C>T (p.P48L) alteration is located in exon 3 (coding exon 2) of the NDC80 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the proline (P) at amino acid position 48 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.9

D;.

REVEL

Benign

0.091

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.018

D;T

Polyphen

0.82

P;.

Vest4

0.30

MutPred

0.61

Gain of MoRF binding (P = 0.0473);Gain of MoRF binding (P = 0.0473);

MVP

0.27

MPC

0.27

ClinPred

0.40

GERP RS

3.5

Varity_R

0.13

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over