14-44962445-G-A

Variant names:

• chr14-44962445-G-A
• NM_001308120.2:c.24G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001308120.2(TOGARAM1):​c.24G>A​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TOGARAM1 NM_001308120.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-44962445-G-A is Benign according to our data. Variant chr14-44962445-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3026845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOGARAM1	NM_001308120.2	c.24G>A	p.Leu8Leu	synonymous_variant	Exon 1 of 20	ENST00000361462.7	NP_001295049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOGARAM1	ENST00000361462.7	c.24G>A	p.Leu8Leu	synonymous_variant	Exon 1 of 20	1	NM_001308120.2	ENSP00000354917.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422076 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TOGARAM1: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-45431648;