Genetic Variant KIAA0753:c.2786+43A>G (chr17-6589736-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.96

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 (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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
KIAA0753	NM_014804.3 link	c.2786+43A>G		intron_variant	Intron 18 of 18	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.2786+43A>G		intron_variant	Intron 18 of 18	1	NM_014804.3	ENSP00000355250.3		Q2KHM9-1

Frequencies

GnomAD3 genomes

AF:

0.987

AC:

150244

AN:

152242

Hom.:

74202

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.987

AC XY:

654583

AN XY:

662888

show subpopulations

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.:

AF XY:

0.987

AC XY:

73497

AN XY:

74490

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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