14-45073835-T-G

Variant names:

• chr14-45073835-T-G
• rs1053667
• NM_001308120.2:c.*274T>G

Variant summary

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

The NM_001308120.2(TOGARAM1):​c.*274T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000697 in 143,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: TOGARAM1 NM_001308120.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

TOGARAM1 (HGNC:19959): (TOG array regulator of axonemal microtubules 1) Predicted to enable microtubule binding activity. Predicted to be involved in organelle assembly and positive regulation of microtubule polymerization. Predicted to be located in ciliary basal body. Predicted to be active in cilium and microtubule cytoskeleton. Predicted to colocalize with microtubule. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

TOGARAM1 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: Franklin by Genoox, G2P
• Joubert syndrome 37

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

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 (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308120.2. 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
	TOGARAM1	NM_001308120.2	MANE Select	c.*274T>G		3_prime_UTR	Exon 20 of 20	NP_001295049.1	G3XAE9
	TOGARAM1	NM_015091.4		c.*274T>G		3_prime_UTR	Exon 19 of 19	NP_055906.2	Q9Y4F4-1
	TOGARAM1	NR_131765.2		n.5659T>G		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM1	ENST00000361462.7	TSL:1 MANE Select	c.*274T>G		3_prime_UTR	Exon 20 of 20	ENSP00000354917.2	G3XAE9
	TOGARAM1	ENST00000361577.7	TSL:1	c.*274T>G		3_prime_UTR	Exon 19 of 19	ENSP00000355045.3	Q9Y4F4-1
	TOGARAM1	ENST00000557423.5	TSL:1	n.*2439T>G		non_coding_transcript_exon	Exon 20 of 20	ENSP00000451829.1	Q9Y4F4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000697 AC: 1 AN: 143496 Hom.: 0 Cov.: 0 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 4624

American (AMR) AF: 0.00 AC: 0 AN: 5728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5208

East Asian (EAS) AF: 0.00 AC: 0 AN: 10672

South Asian (SAS) AF: 0.00 AC: 0 AN: 9240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 656

European-Non Finnish (NFE) AF: 0.0000110 AC: 1 AN: 91120

Other (OTH) AF: 0.00 AC: 0 AN: 9158

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		3.8

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: rs1053667; hg19: chr14-45543038;