Variant 4-55953098-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025009.5(CEP135):c.127A>T(p.Thr43Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,424,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CEP135
NM_025009.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

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 links:

LOC124900705 (HGNC:):

LOC124900705 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
CEP135	NM_025009.5 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	3/26	ENST00000257287.5
LOC124900705	XR_007058124.1 linkuse as main transcript	n.198-627T>A		intron_variant, non_coding_transcript_variant
CEP135	XM_006714055.4 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	3/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP135	ENST00000257287.5 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	3/26	1	NM_025009.5	P1	Q66GS9-1
CEP135	ENST00000422247.6 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	3/6	2			Q66GS9-2
CEP135	ENST00000706800.1 linkuse as main transcript	n.300A>T		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1424512

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708230

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2023

The c.127A>T (p.T43S) alteration is located in exon 3 (coding exon 2) of the CEP135 gene. This alteration results from a A to T substitution at nucleotide position 127, causing the threonine (T) at amino acid position 43 to be replaced by a serine (S). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;T

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

D;N

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.77

MutPred

0.30

Gain of disorder (P = 0.0372);Gain of disorder (P = 0.0372);

MVP

0.78

MPC

0.36

ClinPred

1.0

GERP RS

4.3

Varity_R

0.50

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over