17-6589736-T-C

Variant names:

• chr17-6589736-T-C
• rs367918
• NM_014804.3:c.2786+43A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome XV

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Franklin by Genoox, Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282936 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014804.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	NM_014804.3	MANE Select	c.2786+43A>G		intron	N/A	NP_055619.2	Q2KHM9-1
	KIAA0753	NM_001351225.2		c.1889+43A>G		intron	N/A	NP_001338154.1	Q2KHM9-2
	KIAA0753	NR_147086.2		n.2592+43A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	ENST00000361413.8	TSL:1 MANE Select	c.2786+43A>G		intron	N/A	ENSP00000355250.3	Q2KHM9-1
	ENSG00000282936	ENST00000634965.3	TSL:6	c.*3736+43A>G		intron	N/A	ENSP00000499350.1	A0A590UJ96
	KIAA0753	ENST00000572370.5	TSL:2	c.1889+43A>G		intron	N/A	ENSP00000460050.1	Q2KHM9-2

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

GnomAD2 exomes AF: 0.976 AC: 203074 AN: 207966 AF XY: 0.979

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 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

African (AFR) AF: 0.998 AC: 28986 AN: 29042

American (AMR) AF: 0.956 AC: 32684 AN: 34188

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 22595 AN: 22820

East Asian (EAS) AF: 0.839 AC: 32109 AN: 38282

South Asian (SAS) AF: 0.994 AC: 76099 AN: 76552

European-Finnish (FIN) AF: 0.994 AC: 51699 AN: 52032

Middle Eastern (MID) AF: 0.997 AC: 4150 AN: 4162

European-Non Finnish (NFE) AF: 0.992 AC: 1007113 AN: 1014812

Other (OTH) AF: 0.986 AC: 54351 AN: 55096

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

African (AFR) AF: 0.997 AC: 41452 AN: 41592

American (AMR) AF: 0.979 AC: 14996 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3438 AN: 3472

East Asian (EAS) AF: 0.845 AC: 4376 AN: 5180

South Asian (SAS) AF: 0.993 AC: 4789 AN: 4824

European-Finnish (FIN) AF: 0.995 AC: 10568 AN: 10622

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67450 AN: 68040

Other (OTH) AF: 0.989 AC: 2091 AN: 2114

Alfa AF: 0.985 Hom.: 31732

Bravo AF: 0.984

Asia WGS AF: 0.943 AC: 3280 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.18
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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