chr14-44962508-CG-T

Variant names:

• chr14-44962508-CG-T
• NM_001308120.2:c.87_88delCGinsT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001308120.2(TOGARAM1):​c.87_88delCGinsT​(p.Ala30ProfsTer13) variant causes a frameshift, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOGARAM1 NM_001308120.2 frameshift, synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.809
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.87_88delCGinsT	p.Ala30ProfsTer13	frameshift synonymous	Exon 1 of 20	NP_001295049.1	G3XAE9
	TOGARAM1	NM_015091.4		c.87_88delCGinsT	p.Ala30ProfsTer13	frameshift synonymous	Exon 1 of 19	NP_055906.2	Q9Y4F4-1
	TOGARAM1	NR_131765.2		n.319_320delCGinsT		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.87_88delCGinsT	p.Ala30ProfsTer13	frameshift synonymous	Exon 1 of 20	ENSP00000354917.2	G3XAE9
	TOGARAM1	ENST00000361577.7	TSL:1	c.87_88delCGinsT	p.Ala30ProfsTer13	frameshift synonymous	Exon 1 of 19	ENSP00000355045.3	Q9Y4F4-1
	TOGARAM1	ENST00000555607.1	TSL:1	n.295_296delCGinsT		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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr14-45431711;