chr17-6589759-G-A

Variant names:

• chr17-6589759-G-A
• rs74701712
• NM_014804.3:c.2786+20C>T

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+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,571,708 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (112 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (102 hom.)
• Consequence: KIAA0753 NM_014804.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.158
• Publications: 1 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=-0.85).
• BP6: Variant 17-6589759-G-A is Benign according to our data. Variant chr17-6589759-G-A is described in ClinVar as Benign. ClinVar VariationId is 1248546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 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+20C>T		intron	N/A	NP_055619.2	Q2KHM9-1
	KIAA0753	NM_001351225.2		c.1889+20C>T		intron	N/A	NP_001338154.1	Q2KHM9-2
	KIAA0753	NR_147086.2		n.2592+20C>T		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+20C>T		intron	N/A	ENSP00000355250.3	Q2KHM9-1
	ENSG00000282936	ENST00000634965.3	TSL:6	c.*3736+20C>T		intron	N/A	ENSP00000499350.1	A0A590UJ96
	KIAA0753	ENST00000572370.5	TSL:2	c.1889+20C>T		intron	N/A	ENSP00000460050.1	Q2KHM9-2

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3318 AN: 152148 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00569 AC: 1271 AN: 223258 AF XY: 0.00417

Gnomad AFR exome AF: 0.0748

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000267

Gnomad OTH exome AF: 0.00434

GnomAD4 exome AF: 0.00228 AC: 3236 AN: 1419442 Hom.: 102 Cov.: 28 AF XY: 0.00195 AC XY: 1378 AN XY: 707044

African (AFR) AF: 0.0759 AC: 2369 AN: 31228

American (AMR) AF: 0.00420 AC: 153 AN: 36402

Ashkenazi Jewish (ASJ) AF: 0.00257 AC: 63 AN: 24488

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.000209 AC: 17 AN: 81332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52966

Middle Eastern (MID) AF: 0.00361 AC: 18 AN: 4984

European-Non Finnish (NFE) AF: 0.000240 AC: 262 AN: 1090148

Other (OTH) AF: 0.00604 AC: 354 AN: 58622

GnomAD4 genome AF: 0.0218 AC: 3326 AN: 152266 Hom.: 112 Cov.: 33 AF XY: 0.0211 AC XY: 1569 AN XY: 74456

African (AFR) AF: 0.0744 AC: 3091 AN: 41528

American (AMR) AF: 0.0104 AC: 159 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68026

Other (OTH) AF: 0.0185 AC: 39 AN: 2108

Alfa AF: 0.0112 Hom.: 18

Bravo AF: 0.0254

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		-0.16
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: rs74701712; hg19: chr17-6493079;