rs150331261

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_025009.5(CEP135):c.638T>C(p.Val213Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000392 in 1,614,058 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

CEP135
NM_025009.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 6.52

Publications

3 publications found

Variant links:

Genes affected

CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

CEP135 Gene-Disease associations (from GenCC):

microcephaly 8, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP135 links:

LOC124900705 (HGNC:):

LOC124900705 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029255748).

BP6

Variant 4-55959705-T-C is Benign according to our data. Variant chr4-55959705-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0022 (335/152278) while in subpopulation AFR AF = 0.00756 (314/41556). AF 95% confidence interval is 0.00687. There are 0 homozygotes in GnomAd4. There are 161 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5 link	c.638T>C	p.Val213Ala	missense_variant	Exon 6 of 26	ENST00000257287.5	NP_079285.2	Q66GS9-1
CEP135	XM_006714055.4 link	c.638T>C	p.Val213Ala	missense_variant	Exon 6 of 26		XP_006714118.1
LOC124900705	XR_007058124.1 link	n.198-7234A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP135	ENST00000257287.5 link	c.638T>C	p.Val213Ala	missense_variant	Exon 6 of 26	1	NM_025009.5	ENSP00000257287.3	Q66GS9-1
CEP135	ENST00000422247.6 link	c.638T>C	p.Val213Ala	missense_variant	Exon 6 of 6	2		ENSP00000412799.2	Q66GS9-2
CEP135	ENST00000515081.1 link	n.272T>C		non_coding_transcript_exon_variant	Exon 3 of 5	2
CEP135	ENST00000706800.1 link	n.3128T>C		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000660

AC:

166

AN:

251364

AF XY:

0.000501

show subpopulations

Gnomad AFR exome

AF:

0.00861

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

297

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

120

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00756

AC:

253

AN:

33476

American (AMR)

AF:

0.000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111954

Other (OTH)

AF:

0.000364

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.00220

AC:

335

AN:

152278

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00756

AC:

314

AN:

41556

American (AMR)

AF:

0.000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000902

Hom.:

Bravo

AF:

0.00257

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000881

AC:

107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 22, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly 8, primary, autosomal recessive

Uncertain:1

Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

M;M

PhyloP100

6.5

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.9

D;N

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0080

D;T

Polyphen

0.74

P;P

Vest4

0.41

MVP

0.72

MPC

0.37

ClinPred

0.028

GERP RS

4.8

Varity_R

0.41

gMVP

0.76

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over