chr17-6589878-T-C

Position:

• chr17-6589878-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (32131 hom., cov: 32)
  • Exomes 𝑓: 0.59 (253028 hom.)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.73

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 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
KIAA0753	NM_014804.3	c.2687A>G	p.Gln896Arg	missense_variant	18/19	ENST00000361413.8	NP_055619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0753	ENST00000361413.8	c.2687A>G	p.Gln896Arg	missense_variant	18/19	1	NM_014804.3	ENSP00000355250.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97690 AN: 151938 Hom.: 32078 Cov.: 32

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

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.: 42 AF XY: 0.585 AC XY: 425275 AN XY: 726752

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.: 32 AF XY: 0.644 AC XY: 47835 AN XY: 74330

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

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Short-rib thoracic dysplasia 21 without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Joubert syndrome 38 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Orofaciodigital syndrome XV Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.12
DEOGEN2	Benign	0.00093	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.16	T;T;T
MetaRNN	Benign	0.0000011	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.37	T
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	T
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

Other links and lift over

dbSNP: rs1443417; hg19: chr17-6493198; COSMIC: COSV63816774;