17-6589878-T-G

Variant names:

• chr17-6589878-T-G
• rs1443417
• NM_014804.3:c.2687A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014804.3(KIAA0753):​c.2687A>C​(p.Gln896Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. Q896R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0753 NM_014804.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 41 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11004096).

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.2687A>C	p.Gln896Pro	missense	Exon 18 of 19	NP_055619.2
	KIAA0753	NM_001351225.2		c.1790A>C	p.Gln597Pro	missense	Exon 18 of 19	NP_001338154.1
	KIAA0753	NR_147086.2		n.2493A>C		non_coding_transcript_exon	Exon 16 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0753	ENST00000361413.8	TSL:1 MANE Select	c.2687A>C	p.Gln896Pro	missense	Exon 18 of 19	ENSP00000355250.3
	KIAA0753	ENST00000572370.5	TSL:2	c.1790A>C	p.Gln597Pro	missense	Exon 17 of 18	ENSP00000460050.1
	KIAA0753	ENST00000576281.5	TSL:5	c.275A>C	p.Gln92Pro	missense	Exon 3 of 4	ENSP00000460156.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.021
Sift	Benign	0.060	T
Sift4G	Benign	0.095	T
Polyphen		0.17	B
Vest4		0.18
MutPred		0.43		Gain of loop (P = 0.1069)
MVP		0.11
MPC		0.092
ClinPred		0.092	T
GERP RS		2.4
Varity_R		0.22
gMVP		0.57

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: rs1443417; hg19: chr17-6493198;