14-44962567-AC-GT

Variant names:

• chr14-44962567-AC-GT
• NM_001308120.2:c.146_147delACinsGT
• TOGARAM1 p.Tyr49Cys

Variant summary

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

The NM_001308120.2(TOGARAM1):​c.146_147delACinsGT​(p.Tyr49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOGARAM1 NM_001308120.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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]

KLHL28 (HGNC:19741): (kelch like family member 28)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.146_147delACinsGT	p.Tyr49Cys	missense	N/A	NP_001295049.1	G3XAE9
	TOGARAM1	NM_015091.4		c.146_147delACinsGT	p.Tyr49Cys	missense	N/A	NP_055906.2	Q9Y4F4-1
	TOGARAM1	NR_131765.2		n.378_379delACinsGT		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM1	ENST00000361462.7	TSL:1 MANE Select	c.146_147delACinsGT	p.Tyr49Cys	missense	N/A	ENSP00000354917.2	G3XAE9
	TOGARAM1	ENST00000361577.7	TSL:1	c.146_147delACinsGT	p.Tyr49Cys	missense	N/A	ENSP00000355045.3	Q9Y4F4-1
	TOGARAM1	ENST00000555607.1	TSL:1	n.354_355delACinsGT		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

hg19: chr14-45431770;