Variant chr19-32879178-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032816.5(CEP89):c.2336A>T(p.His779Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,608,210 control chromosomes in the GnomAD database, including 89,299 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5482 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83817 hom. )

Consequence

CEP89
NM_032816.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.376

Variant links:

Genes affected

CEP89 (HGNC:25907): (centrosomal protein 89) Involved in non-motile cilium assembly. Acts upstream of or within cilium assembly. Located in several cellular components, including cytosol; microtubule cytoskeleton; and non-motile cilium. Part of ciliary transition fiber. [provided by Alliance of Genome Resources, Apr 2022]

CEP89 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061840713).

BP6

Variant 19-32879178-T-A is Benign according to our data. Variant chr19-32879178-T-A is described in ClinVar as [Benign]. Clinvar id is 1579631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CEP89	NM_032816.5 linkuse as main transcript	c.2336A>T	p.His779Leu	missense_variant	19/19	ENST00000305768.10
CEP89	XM_005259344.4 linkuse as main transcript	c.2264A>T	p.His755Leu	missense_variant	19/19
CEP89	XM_047439562.1 linkuse as main transcript	c.1595A>T	p.His532Leu	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP89	ENST00000305768.10 linkuse as main transcript	c.2336A>T	p.His779Leu	missense_variant	19/19	1	NM_032816.5	P3	Q96ST8-1
CEP89	ENST00000586984.6 linkuse as main transcript	c.*945A>T		3_prime_UTR_variant, NMD_transcript_variant	18/18	1
CEP89	ENST00000591698.5 linkuse as main transcript	c.*1670A>T		3_prime_UTR_variant, NMD_transcript_variant	18/18	2

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37506

AN:

151876

Hom.:

5485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.261

AC:

64970

AN:

249174

Hom.:

9720

AF XY:

0.268

AC XY:

36058

AN XY:

134636

show subpopulations

Gnomad AFR exome

AF:

0.0980

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.329

AC:

478996

AN:

1456216

Hom.:

83817

Cov.:

AF XY:

0.326

AC XY:

235919

AN XY:

723728

show subpopulations

Gnomad4 AFR exome

AF:

0.0932

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.0923

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.247

AC:

37502

AN:

151994

Hom.:

5482

Cov.:

AF XY:

0.241

AC XY:

17876

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.352

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.326

Hom.:

6534

Bravo

AF:

0.234

TwinsUK

AF:

0.371

AC:

1377

ALSPAC

AF:

0.367

AC:

1414

ESP6500AA

AF:

0.109

AC:

481

ESP6500EA

AF:

0.355

AC:

3052

ExAC

AF:

0.264

AC:

32038

Asia WGS

AF:

0.131

AC:

457

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.344

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.12

DANN

Benign

0.23

DEOGEN2

Benign

0.0019

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.55

REVEL

Benign

0.018

Sift

Benign

0.70

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.037

MPC

0.13

ClinPred

0.0029

GERP RS

-4.7

Varity_R

0.056

gMVP

0.039

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

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