1-3836504-T-C

Variant names:

• chr1-3836504-T-C
• rs148455387
• NM_014704.4:c.1308A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014704.4(CEP104):​c.1308A>G​(p.Gly436Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G436G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP104 NM_014704.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 1 publications found

Genes affected

CEP104 (HGNC:24866): (centrosomal protein 104) This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. [provided by RefSeq, Feb 2016]

CEP104 Gene-Disease associations (from GenCC):

• Joubert syndrome 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014704.4. 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
	CEP104	NM_014704.4	MANE Select	c.1308A>G	p.Gly436Gly	synonymous	Exon 10 of 22	NP_055519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP104	ENST00000378230.8	TSL:5 MANE Select	c.1308A>G	p.Gly436Gly	synonymous	Exon 10 of 22	ENSP00000367476.3
	CEP104	ENST00000494653.5	TSL:1	c.1308A>G	p.Gly436Gly	synonymous	Exon 10 of 12	ENSP00000501736.1
	CEP104	ENST00000675666.1		c.1308A>G	p.Gly436Gly	synonymous	Exon 10 of 21	ENSP00000502548.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 129954 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1257492 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 631532

African (AFR) AF: 0.00 AC: 0 AN: 24808

American (AMR) AF: 0.00 AC: 0 AN: 42658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22346

East Asian (EAS) AF: 0.00 AC: 0 AN: 34566

South Asian (SAS) AF: 0.00 AC: 0 AN: 80948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 951230

Other (OTH) AF: 0.00 AC: 0 AN: 50808

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 129954 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 61712

African (AFR) AF: 0.00 AC: 0 AN: 35272

American (AMR) AF: 0.00 AC: 0 AN: 11492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3244

East Asian (EAS) AF: 0.00 AC: 0 AN: 3934

South Asian (SAS) AF: 0.00 AC: 0 AN: 3744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62418

Other (OTH) AF: 0.00 AC: 0 AN: 1704

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.0040
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148455387; hg19: chr1-3753068;