Variant chr17-81190986-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014984.4(CEP131):c.2864T>C(p.Leu955Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000871 in 1,608,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CEP131
NM_014984.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

CEP131 (HGNC:29511): (centrosomal protein 131) Enables protein homodimerization activity. Involved in several processes, including intraciliary transport involved in cilium assembly; protein localization to centrosome; and regulation of centrosome duplication. Located in several cellular components, including ciliary transition zone; intercellular bridge; and microtubule organizing center. Colocalizes with centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP131 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CEP131	NM_014984.4 linkuse as main transcript	c.2864T>C	p.Leu955Pro	missense_variant	23/26	ENST00000450824.7	NP_055799.2	Q9UPN4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7 linkuse as main transcript	c.2864T>C	p.Leu955Pro	missense_variant	23/26	1	NM_014984.4	ENSP00000393583.2		Q9UPN4-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

246018

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133902

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000547

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000824

AC:

AN:

1455762

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724438

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Apr 07, 2023

The c.2864T>C (p.L955P) alteration is located in exon 23 (coding exon 22) of the CEP131 gene. This alteration results from a T to C substitution at nucleotide position 2864, causing the leucine (L) at amino acid position 955 to be replaced by a proline (P). 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

Pathogenic

0.81

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.;.;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;D;D;D;T

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

.;M;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.3

D;D;.;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D;.;D;.

Sift4G

Benign

0.088

T;T;T;T;T

Polyphen

1.0

D;D;.;D;.

Vest4

0.58

MVP

0.56

MPC

0.58

ClinPred

0.93

GERP RS

4.1

Varity_R

0.88

gMVP

0.76

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