1-10430542-G-A

Position:

chr1-10430542-G-A

Variant summary

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

The ENST00000309048.8(CENPS):c.25G>A(p.Glu9Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,556 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: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CENPS
ENST00000309048.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

CENPS (HGNC:23163): (centromere protein S) This gene was identified in the neuroblastoma tumor suppressor candidate region on chromosome 1p36. It contains a TFIID-31 domain, similar to that found in TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. This gene was expressed at very low levels in neuroblastoma tumors, and was shown to reduce cell growth in neuroblastoma cells, suggesting that it may have a role in a cell death pathway. The protein is a component of multiple complexes, including the Fanconi anemia (FA) core complex, the APITD1/CENPS complex, and the CENPA-CAD (nucleosome distal) complex. Known functions include an involvement with chromatin associations of the FA core complex, and a role in the stable assembly of the outer kinetochore. Alternative splicing of this gene results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream cortistatin (CORT) gene, as represented in GeneID:100526739. An APITD1-related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2010]

CENPS links:

(HGNC:):

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=0.13629276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CENPS	NM_199294.3 linkuse as main transcript	c.25G>A	p.Glu9Lys	missense_variant	1/5	ENST00000309048.8	NP_954988.1
CENPS-CORT	NM_198544.4 linkuse as main transcript	c.25G>A	p.Glu9Lys	missense_variant	1/5		NP_940946.1
CENPS-CORT	NM_001270517.2 linkuse as main transcript	c.25G>A	p.Glu9Lys	missense_variant	1/6		NP_001257446.1
CENPS-CORT	NM_199006.3 linkuse as main transcript	c.25G>A	p.Glu9Lys	missense_variant	1/4		NP_950171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPS	ENST00000309048.8 linkuse as main transcript	c.25G>A	p.Glu9Lys	missense_variant	1/5	1	NM_199294.3	ENSP00000308583	P1	Q8N2Z9-1
	ENST00000607572.1 linkuse as main transcript	n.136C>T		non_coding_transcript_exon_variant	1/1
CENPS	ENST00000602486.1 linkuse as main transcript	n.31G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000150

AC:

AN:

133512

Hom.:

AF XY:

0.0000141

AC XY:

AN XY:

71084

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:

0.0000473

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000263

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1383556

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682402

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000257

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Feb 10, 2022

The c.25G>A (p.E9K) alteration is located in exon 1 (coding exon 1) of the APITD1-CORT gene. This alteration results from a G to A substitution at nucleotide position 25, causing the glutamic acid (E) at amino acid position 9 to be replaced by a lysine (K). 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

0.16

BayesDel_addAF

Benign

-0.0060

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;.;.;T

Eigen

Benign

0.054

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.55

T;T;T;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;.;.;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.13

T;D;.;D

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.70

.;.;.;P

Vest4

0.25

MutPred

0.26

Gain of ubiquitination at E9 (P = 0.0037);Gain of ubiquitination at E9 (P = 0.0037);Gain of ubiquitination at E9 (P = 0.0037);Gain of ubiquitination at E9 (P = 0.0037);

MVP

0.030

MPC

0.020

ClinPred

0.85

GERP RS

3.9

Varity_R

0.50

gMVP

0.37

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