chr17-6589878-T-C

Variant names:

Variant summary

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

The NM_014804.3(KIAA0753):c.2687A>G(p.Gln896Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,612,958 control chromosomes in the GnomAD database, including 285,159 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.64 ( 32131 hom., cov: 32)

Exomes 𝑓: 0.59 ( 253028 hom. )

Consequence

KIAA0753
NM_014804.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

KIAA0753 (HGNC:29110): (KIAA0753) This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]

KIAA0753 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=1.0560783E-6).

BP6

Variant 17-6589878-T-C is Benign according to our data. Variant chr17-6589878-T-C is described in ClinVar as [Benign]. Clinvar id is 1236419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0753	NM_014804.3 link	c.2687A>G	p.Gln896Arg	missense_variant	Exon 18 of 19	ENST00000361413.8	NP_055619.2	Q2KHM9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0753	ENST00000361413.8 link	c.2687A>G	p.Gln896Arg	missense_variant	Exon 18 of 19	1	NM_014804.3	ENSP00000355250.3		Q2KHM9-1

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97690

AN:

151938

Hom.:

32078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.609

GnomAD3 exomes

AF:

0.622

AC:

154948

AN:

248926

Hom.:

49249

AF XY:

0.614

AC XY:

82952

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.702

Gnomad SAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.585

AC:

855263

AN:

1460902

Hom.:

253028

Cov.:

AF XY:

0.585

AC XY:

425275

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.784

Gnomad4 AMR exome

AF:

0.737

Gnomad4 ASJ exome

AF:

0.514

Gnomad4 EAS exome

AF:

0.725

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.567

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.643

AC:

97792

AN:

152056

Hom.:

32131

Cov.:

AF XY:

0.644

AC XY:

47835

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.716

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.613

Alfa

AF:

0.581

Hom.:

64074

Bravo

AF:

0.659

TwinsUK

AF:

0.565

AC:

2094

ALSPAC

AF:

0.572

AC:

2205

ESP6500AA

AF:

0.779

AC:

2960

ESP6500EA

AF:

0.574

AC:

4733

ExAC

AF:

0.622

AC:

75185

Asia WGS

AF:

0.697

AC:

2429

AN:

3478

EpiCase

AF:

0.565

EpiControl

AF:

0.561

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Short-rib thoracic dysplasia 21 without polydactyly

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 38

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Orofaciodigital syndrome XV

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.12

DEOGEN2

Benign

0.00093

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

0.0000011

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.84

.;N;.

REVEL

Benign

0.014

Sift

Benign

0.35

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.028, 0.019

MPC

0.081

ClinPred

0.0029

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.015

gMVP

0.25

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