Variant 17-64510258-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001316990.2(CEP95):c.-153G>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000619 in 1,455,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 1 hom. )

Consequence

CEP95
NM_001316990.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

CEP95 (HGNC:25141): (centrosomal protein 95) Located in centrosome and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

CEP95 links:

CEP95 (HGNC:):

CEP95 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP95	NM_138363.3 linkuse as main transcript	c.234G>T	p.Gln78His	missense_variant	3/20	ENST00000556440.7	NP_612372.1	Q96GE4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP95	ENST00000556440.7 linkuse as main transcript	c.234G>T	p.Gln78His	missense_variant	3/20	1	NM_138363.3	ENSP00000450461.2		Q96GE4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

243932

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132194

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:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1455090

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723870

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:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

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

Jan 17, 2024

The c.234G>T (p.Q78H) alteration is located in exon 3 (coding exon 3) of the CEP95 gene. This alteration results from a G to T substitution at nucleotide position 234, causing the glutamine (Q) at amino acid position 78 to be replaced by a histidine (H). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

T;.;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Pathogenic

0.93

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.0

N;.;.

REVEL

Uncertain

0.58

Sift

Benign

0.059

T;.;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.80

MutPred

0.67

Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.86

MPC

0.19

ClinPred

0.31

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.63

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