chr1-10430550-G-T

Position:

chr1-10430550-G-T

Variant summary

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

The NM_199294.3(CENPS):c.33G>T(p.Gln11His) 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 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CENPS
NM_199294.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

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:

CENPS-CORT (HGNC:38843): (CENPS-CORT readthrough) This locus represents naturally occurring read-through transcription between the neighboring APITD1 (apoptosis-inducing, TAF9-like domain 1) and CORT (cortistatin) genes. Alternative splicing results in multiple transcript variants, two of which encode fusion proteins that share sequence identity with the products of each individual gene. [provided by RefSeq, Aug 2011]

CENPS-CORT links:

CENPS (HGNC:):

CENPS 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=0.11758813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPS	NM_199294.3 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/5	ENST00000309048.8	NP_954988.1	Q8N2Z9-1
CENPS-CORT	NM_198544.4 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/5		NP_940946.1	Q8N2Z9-2
CENPS-CORT	NM_001270517.2 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/6		NP_001257446.1	Q8N2Z9-1
CENPS-CORT	NM_199006.3 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/4		NP_950171.2	Q8N2Z9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPS	ENST00000309048.8 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/5	1	NM_199294.3	ENSP00000308583.2		Q8N2Z9-1
CENPS-CORT	ENST00000602787.6 linkuse as main transcript	c.33G>T	p.Gln11His	missense_variant	1/6	3		ENSP00000473509.2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1382820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682050

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

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 30, 2024

The c.33G>T (p.Q11H) alteration is located in exon 1 (coding exon 1) of the APITD1-CORT gene. This alteration results from a G to T substitution at nucleotide position 33, causing the glutamine (Q) at amino acid position 11 to be replaced by a histidine (H). 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

0.19

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

.;.;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.45

T;T;T;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;.;L

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.80

N;N;.;N

REVEL

Benign

0.11

Sift

Benign

0.094

T;D;.;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.84

.;.;.;P

Vest4

0.16

MutPred

0.10

Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.014

MPC

0.13

ClinPred

0.70

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.22

gMVP

0.14

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