17-6623043-G-C

Variant names:

• chr17-6623043-G-C
• rs762771340
• NM_014804.3:c.943C>G
• KIAA0753 p.Gln315Glu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014804.3(KIAA0753):​c.943C>G​(p.Gln315Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q315R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.20
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.943C>G	p.Gln315Glu	missense	Exon 6 of 19	NP_055619.2	Q2KHM9-1
	KIAA0753	NM_001351225.2		c.46C>G	p.Gln16Glu	missense	Exon 6 of 19	NP_001338154.1	Q2KHM9-2
	KIAA0753	NR_147086.2		n.979C>G		non_coding_transcript_exon	Exon 5 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	ENST00000361413.8	TSL:1 MANE Select	c.943C>G	p.Gln315Glu	missense	Exon 6 of 19	ENSP00000355250.3	Q2KHM9-1
	KIAA0753	ENST00000572370.5	TSL:2	c.46C>G	p.Gln16Glu	missense	Exon 5 of 18	ENSP00000460050.1	Q2KHM9-2
	ENSG00000282936	ENST00000634965.3	TSL:6	c.*1893C>G		3_prime_UTR	Exon 6 of 19	ENSP00000499350.1	A0A590UJ96

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
PhyloP100		8.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.27	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.31
Mutation Taster		=78/22	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs762771340;

hg19: chr17-6526363;