Genetic Variant CEP295:p.Thr2591Arg (chr11-93730235-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033395.2(CEP295):c.7772C>G(p.Thr2591Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,551,112 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CEP295
NM_033395.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Publications

0 publications found

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:

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

TAF1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21458054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033395.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP295	NM_033395.2	MANE Select	c.7772C>G	p.Thr2591Arg	missense	Exon 30 of 30	NP_203753.1	Q9C0D2-1
TAF1D	NR_146090.2		n.1696G>C		non_coding_transcript_exon	Exon 14 of 14
TAF1D	NR_146091.2		n.1588G>C		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP295	ENST00000325212.11	TSL:2 MANE Select	c.7772C>G	p.Thr2591Arg	missense	Exon 30 of 30	ENSP00000316681.6	Q9C0D2-1
TAF1D	ENST00000526015.5	TSL:1	n.*658G>C		non_coding_transcript_exon	Exon 14 of 14	ENSP00000435087.1	Q9H5J8
TAF1D	ENST00000526015.5	TSL:1	n.*658G>C		3_prime_UTR	Exon 14 of 14	ENSP00000435087.1	Q9H5J8

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000638

AC:

AN:

156694

AF XY:

0.0000603

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1398894

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

689962

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31566

American (AMR)

AF:

0.000421

AC:

AN:

35654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25170

East Asian (EAS)

AF:

0.00

AC:

AN:

35694

South Asian (SAS)

AF:

0.00

AC:

AN:

79214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078812

Other (OTH)

AF:

0.0000345

AC:

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41546

American (AMR)

AF:

0.000523

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

PhyloP100

1.6

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

REVEL

Benign

0.093

Sift

Uncertain

0.0030

Sift4G

Benign

0.093

Polyphen

1.0

Vest4

0.43

MVP

0.072

MPC

0.40

ClinPred

0.30

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.46

gMVP

0.30

Mutation Taster

=83/17

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over