Genetic Variant CEP250:p.Ala36Ser (chr20-35462473-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007186.6(CEP250):c.106G>T(p.Ala36Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A36T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP250
NM_007186.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.29

Publications

1 publications found

Variant links:

Genes affected

CEP250 (HGNC:1859): (centrosomal protein 250) This gene encodes a core centrosomal protein required for centriole-centriole cohesion during interphase of the cell cycle. The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

CEP250 Gene-Disease associations (from GenCC):

cone-rod dystrophy and hearing loss 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

CEP250 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34866846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007186.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	NM_007186.6	MANE Select	c.106G>T	p.Ala36Ser	missense	Exon 4 of 35	NP_009117.2
	CEP250	NM_001318219.1		c.-1794G>T		5_prime_UTR	Exon 2 of 33	NP_001305148.1	Q9BV73

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP250	ENST00000397527.6	TSL:5 MANE Select	c.106G>T	p.Ala36Ser	missense	Exon 4 of 35	ENSP00000380661.1	Q9BV73-1
CEP250	ENST00000446710.5	TSL:1	c.106G>T	p.Ala36Ser	missense	Exon 4 of 7	ENSP00000398747.1	Q5JWS5
CEP250	ENST00000706828.1		c.106G>T	p.Ala36Ser	missense	Exon 4 of 36	ENSP00000516576.1	A0A9L9PXX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724142

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

85216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109548

Other (OTH)

AF:

0.00

AC:

AN:

60160

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

M_CAP

Benign

0.011

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.1

PhyloP100

5.3

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.21

Sift

Benign

0.16

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.25

MutPred

0.32

Gain of methylation at K41 (P = 0.1011)

MVP

0.59

MPC

0.59

ClinPred

0.91

GERP RS

5.1

PromoterAI

-0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.097

Mutation Taster

=56/44

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over