Variant 11-93679422-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_033395.2(CEP295):c.635G>A(p.Arg212His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,396,710 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CEP295
NM_033395.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CEP295 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020623088).

BP6

Variant 11-93679422-G-A is Benign according to our data. Variant chr11-93679422-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2330572.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295	NM_033395.2 linkuse as main transcript	c.635G>A	p.Arg212His	missense_variant	7/30	ENST00000325212.11	NP_203753.1	Q9C0D2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11 linkuse as main transcript	c.635G>A	p.Arg212His	missense_variant	7/30	2	NM_033395.2	ENSP00000316681.6		Q9C0D2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1396710

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

688824

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.0064

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.70

M_CAP

Benign

0.0094

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.24

PROVEAN

Benign

2.4

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.62

Polyphen

0.0010

Vest4

0.083

MutPred

0.33

Gain of methylation at K207 (P = 0.0713);

MVP

0.014

MPC

0.10

ClinPred

0.17

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.031

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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