rs367918

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-6589736-T-A
• chr17-6589736-T-C
• chr17-6589736-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014804.3(KIAA0753):​c.2786+43A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA0753 NM_014804.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>T		intron	N/A	NP_055619.2	Q2KHM9-1
	KIAA0753	NM_001351225.2		c.1889+43A>T		intron	N/A	NP_001338154.1	Q2KHM9-2
	KIAA0753	NR_147086.2		n.2592+43A>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+43A>T		intron	N/A	ENSP00000355250.3	Q2KHM9-1
	ENSG00000282936	ENST00000634965.3	TSL:6	c.*3736+43A>T		intron	N/A	ENSP00000499350.1	A0A590UJ96
	KIAA0753	ENST00000572370.5	TSL:2	c.1889+43A>T		intron	N/A	ENSP00000460050.1	Q2KHM9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327122 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 662950

African (AFR) AF: 0.00 AC: 0 AN: 29044

American (AMR) AF: 0.00 AC: 0 AN: 34194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22822

East Asian (EAS) AF: 0.00 AC: 0 AN: 38316

South Asian (SAS) AF: 0.00 AC: 0 AN: 76560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4162

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014886

Other (OTH) AF: 0.00 AC: 0 AN: 55104

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.24
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;