14-45073835-T-C

Variant names:

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

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
• Publications: 28 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]

TOGARAM1 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: Franklin by Genoox, G2P
• Joubert syndrome 37

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

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.

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.*274T>C		3_prime_UTR	Exon 20 of 20	NP_001295049.1	G3XAE9
	TOGARAM1	NM_015091.4		c.*274T>C		3_prime_UTR	Exon 19 of 19	NP_055906.2	Q9Y4F4-1
	TOGARAM1	NR_131765.2		n.5659T>C		non_coding_transcript_exon	Exon 20 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM1	ENST00000361462.7	TSL:1 MANE Select	c.*274T>C		3_prime_UTR	Exon 20 of 20	ENSP00000354917.2	G3XAE9
	TOGARAM1	ENST00000361577.7	TSL:1	c.*274T>C		3_prime_UTR	Exon 19 of 19	ENSP00000355045.3	Q9Y4F4-1
	TOGARAM1	ENST00000557423.5	TSL:1	n.*2439T>C		non_coding_transcript_exon	Exon 20 of 20	ENSP00000451829.1	Q9Y4F4-3

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

African (AFR) AF: 0.222 AC: 1020 AN: 4602

American (AMR) AF: 0.0701 AC: 401 AN: 5722

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 483 AN: 5204

East Asian (EAS) AF: 0.148 AC: 1576 AN: 10648

South Asian (SAS) AF: 0.0912 AC: 842 AN: 9230

European-Finnish (FIN) AF: 0.0888 AC: 628 AN: 7074

Middle Eastern (MID) AF: 0.0625 AC: 41 AN: 656

European-Non Finnish (NFE) AF: 0.0526 AC: 4788 AN: 91030

Other (OTH) 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

African (AFR) AF: 0.229 AC: 9528 AN: 41522

American (AMR) AF: 0.0757 AC: 1158 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 303 AN: 3466

East Asian (EAS) AF: 0.120 AC: 623 AN: 5184

South Asian (SAS) AF: 0.101 AC: 486 AN: 4826

European-Finnish (FIN) AF: 0.0808 AC: 856 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3748 AN: 68030

Other (OTH) AF: 0.105 AC: 221 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		3.8
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

Other links and lift over

dbSNP: rs1053667; hg19: chr14-45543038;