17-6579726-T-C

Position:

• chr17-6579726-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.*21A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,534,580 control chromosomes in the GnomAD database, including 272,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32152 hom., cov: 32)
  • Exomes 𝑓: 0.59 (240182 hom.)
• Consequence: KIAA0753 NM_014804.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.187

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 (BayesDel_noAF=-0.83).
• BP6: Variant 17-6579726-T-C is Benign according to our data. Variant chr17-6579726-T-C is described in ClinVar as [Benign]. Clinvar id is 1259547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0753	NM_014804.3	c.*21A>G		3_prime_UTR_variant	19/19	ENST00000361413.8	NP_055619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0753	ENST00000361413	c.*21A>G		3_prime_UTR_variant	19/19	1	NM_014804.3	ENSP00000355250.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97743 AN: 151962 Hom.: 32099 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.666

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: 0.627

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.610

GnomAD3 exomes AF: 0.623 AC: 153905 AN: 247182 Hom.: 48913 AF XY: 0.614 AC XY: 82420 AN XY: 134208

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.701

Gnomad SAS exome AF: 0.637

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.586 AC: 810193 AN: 1382500 Hom.: 240182 Cov.: 20 AF XY: 0.586 AC XY: 405264 AN XY: 691990

Gnomad4 AFR exome AF: 0.782

Gnomad4 AMR exome AF: 0.737

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.724

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.643 AC: 97845 AN: 152080 Hom.: 32152 Cov.: 32 AF XY: 0.644 AC XY: 47852 AN XY: 74338

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.681

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: 0.577 Hom.: 35114

Bravo AF: 0.659

Asia WGS AF: 0.697 AC: 2430 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.67

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: rs3744720; hg19: chr17-6483046; COSMIC: COSV63817482;