rs1053667

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-45073835-T-C
• chr14-45073835-T-G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TOGARAM1	NM_001308120.2	c.*274T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000361462.7	NP_001295049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOGARAM1	ENST00000361462.7	c.*274T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_001308120.2	ENSP00000354917.2

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 AC: 1020 AN: 4602

Gnomad4 AMR exome AF: 0.0701 AC: 401 AN: 5722

Gnomad4 ASJ exome AF: 0.0928 AC: 483 AN: 5204

Gnomad4 EAS exome AF: 0.148 AC: 1576 AN: 10648

Gnomad4 SAS exome AF: 0.0912 AC: 842 AN: 9230

Gnomad4 FIN exome AF: 0.0888 AC: 628 AN: 7074

Gnomad4 NFE exome AF: 0.0526 AC: 4788 AN: 91030

Gnomad4 Remaining exome AF: 0.0709 AC: 648 AN: 9146

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 AC: 0.229469 AN: 0.229469

Gnomad4 AMR AF: 0.0757 AC: 0.0757259 AN: 0.0757259

Gnomad4 ASJ AF: 0.0874 AC: 0.0874207 AN: 0.0874207

Gnomad4 EAS AF: 0.120 AC: 0.120177 AN: 0.120177

Gnomad4 SAS AF: 0.101 AC: 0.100705 AN: 0.100705

Gnomad4 FIN AF: 0.0808 AC: 0.0808157 AN: 0.0808157

Gnomad4 NFE AF: 0.0551 AC: 0.0550933 AN: 0.0550933

Gnomad4 OTH AF: 0.105 AC: 0.104541 AN: 0.104541

Alfa AF: 0.0744 Hom.: 2405

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
Mutation Taster		=100/0	polymorphism (auto)

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;