rs1053667

Positions:

• chr14-45073835-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001308120.2(TOGARAM1):​c.*274T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.093 in 295,544 control chromosomes in the GnomAD database, including 1,944 homozygotes. 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: 𝑓 0.11 (1386 hom., cov: 32)
  • Exomes 𝑓: 0.073 (558 hom.)
• Consequence: TOGARAM1 NM_001308120.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOGARAM1	NM_001308120.2	c.*274T>C		3_prime_UTR_variant	20/20	ENST00000361462.7	NP_001295049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOGARAM1	ENST00000361462.7	c.*274T>C		3_prime_UTR_variant	20/20	1	NM_001308120.2	ENSP00000354917	P1
TOGARAM1	ENST00000361577.7	c.*274T>C		3_prime_UTR_variant	19/19	1		ENSP00000355045
TOGARAM1	ENST00000557423.5	c.*2439T>C		3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000451829
TOGARAM1	ENST00000556823.1			downstream_gene_variant		3		ENSP00000450465

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16992 AN: 152114 Hom.: 1375 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0728 AC: 10427 AN: 143312 Hom.: 558 Cov.: 0 AF XY: 0.0714 AC XY: 5306 AN XY: 74286

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0701

Gnomad4 ASJ exome AF: 0.0928

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0888

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.0709

GnomAD4 genome AF: 0.112 AC: 17044 AN: 152232 Hom.: 1386 Cov.: 32 AF XY: 0.112 AC XY: 8349 AN XY: 74440

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.0874

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0657 Hom.: 771

Bravo AF: 0.117

Asia WGS AF: 0.110 AC: 383 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs1053667; hg19: chr14-45543038;