rs73342622

Variant names:

• chr17-6596178-G-A
• rs73342622
• NM_014804.3:c.2338C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6596178-G-A
• chr17-6596178-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014804.3(KIAA0753):​c.2338C>T​(p.Arg780Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,770 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30
• Publications: 6 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: Orphanet, Franklin by Genoox
• 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 (MetaRNN=0.007510096).
• BP6: Variant 17-6596178-G-A is Benign according to our data. Variant chr17-6596178-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (1578/152244) while in subpopulation AFR AF = 0.035 (1454/41524). AF 95% confidence interval is 0.0335. There are 30 homozygotes in GnomAd4. There are 778 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	NM_014804.3	MANE Select	c.2338C>T	p.Arg780Cys	missense	Exon 15 of 19	NP_055619.2
	KIAA0753	NM_001351225.2		c.1441C>T	p.Arg481Cys	missense	Exon 15 of 19	NP_001338154.1
	KIAA0753	NR_147086.2		n.2144C>T		non_coding_transcript_exon	Exon 13 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	ENST00000361413.8	TSL:1 MANE Select	c.2338C>T	p.Arg780Cys	missense	Exon 15 of 19	ENSP00000355250.3
	KIAA0753	ENST00000572370.5	TSL:2	c.1441C>T	p.Arg481Cys	missense	Exon 14 of 18	ENSP00000460050.1
	KIAA0753	ENST00000542826.6	TSL:2	n.*776C>T		non_coding_transcript_exon	Exon 8 of 12	ENSP00000444946.3

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1567 AN: 152126 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00264 AC: 657 AN: 248982 AF XY: 0.00199

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00113 AC: 1649 AN: 1461526 Hom.: 25 Cov.: 32 AF XY: 0.000992 AC XY: 721 AN XY: 727064

African (AFR) AF: 0.0364 AC: 1218 AN: 33472

American (AMR) AF: 0.00280 AC: 125 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5762

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1111734

Other (OTH) AF: 0.00267 AC: 161 AN: 60370

GnomAD4 genome AF: 0.0104 AC: 1578 AN: 152244 Hom.: 30 Cov.: 32 AF XY: 0.0105 AC XY: 778 AN XY: 74406

African (AFR) AF: 0.0350 AC: 1454 AN: 41524

American (AMR) AF: 0.00608 AC: 93 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00453 Hom.: 21

Bravo AF: 0.0120

ESP6500AA AF: 0.0307 AC: 122

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00317 AC: 383

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Orofaciodigital syndrome XV;C5561958:Joubert syndrome 38;C5561961:Short-rib thoracic dysplasia 21 without polydactyly Benign:1

May 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.092
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.016	D
Polyphen		0.95	P
Vest4		0.20
MVP		0.50
MPC		0.25
ClinPred		0.030	T
GERP RS		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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: rs73342622; hg19: chr17-6499498;