Variant 17-81190769-G-C 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_014984.4(CEP131):c.2977C>G(p.Leu993Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CEP131
NM_014984.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.123943925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP131	NM_014984.4 linkuse as main transcript	c.2977C>G	p.Leu993Val	missense_variant	24/26	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.2977C>G	p.Leu993Val	missense_variant	24/26	1	NM_014984.4	ENSP00000393583.2		Q9UPN4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246468

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134152

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459544

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726036

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

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

May 26, 2022

The c.2977C>G (p.L993V) alteration is located in exon 24 (coding exon 23) of the CEP131 gene. This alteration results from a C to G substitution at nucleotide position 2977, causing the leucine (L) at amino acid position 993 to be replaced by a valine (V). 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

0.088

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.072

.;T;.;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;.;N;.

REVEL

Benign

0.13

Sift

Benign

0.29

T;T;.;T;.

Sift4G

Benign

0.36

T;T;T;T;T

Polyphen

0.20

B;B;.;B;.

Vest4

0.24

MutPred

0.14

.;Gain of MoRF binding (P = 0.1246);.;.;.;

MVP

0.39

MPC

0.096

ClinPred

0.11

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.17

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