17-6589736-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014804.3(KIAA0753):c.2786+43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,479,346 control chromosomes in the GnomAD database, including 721,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74264 hom., cov: 33)
  • Exomes 𝑓: 0.99 (646915 hom.)
• Consequence: KIAA0753 NM_014804.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.96

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-6589736-T-C is Benign according to our data. Variant chr17-6589736-T-C is described in ClinVar as [Benign]. Clinvar id is 1239632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0753	NM_014804.3	c.2786+43A>G		intron_variant		ENST00000361413.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0753	ENST00000361413.8	c.2786+43A>G		intron_variant		1	NM_014804.3	P1

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150244 AN: 152242 Hom.: 74202 Cov.: 33

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.995

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.989

GnomAD3 exomes AF: 0.976 AC: 203074 AN: 207966 Hom.: 99343 AF XY: 0.979 AC XY: 110744 AN XY: 113096

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 0.953

Gnomad ASJ exome AF: 0.992

Gnomad EAS exome AF: 0.842

Gnomad SAS exome AF: 0.994

Gnomad FIN exome AF: 0.994

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.984

GnomAD4 exome AF: 0.987 AC: 1309786 AN: 1326986 Hom.: 646915 Cov.: 18 AF XY: 0.987 AC XY: 654583 AN XY: 662888

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.956

Gnomad4 ASJ exome AF: 0.990

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.994

Gnomad4 NFE exome AF: 0.992

Gnomad4 OTH exome AF: 0.986

GnomAD4 genome AF: 0.987 AC: 150366 AN: 152360 Hom.: 74264 Cov.: 33 AF XY: 0.987 AC XY: 73497 AN XY: 74490

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.993

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.989

Alfa AF: 0.989 Hom.: 19719

Bravo AF: 0.984

Asia WGS AF: 0.943 AC: 3280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.48
Dann	Benign	0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs367918; hg19: chr17-6493056; COSMIC: COSV63817380; COSMIC: COSV63817380;