dbSNP rs1053667: TOGARAM1:n.*2439T>C (chr14-45073835-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000557423.5(TOGARAM1):n.*2439T>C variant causes a non coding transcript exon 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
ENST00000557423.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

28 publications found

Variant links:

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: G2P, Franklin by Genoox
Joubert syndrome 37
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

TOGARAM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	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 link	c.*274T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_001308120.2	ENSP00000354917.2		G3XAE9

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16992

AN:

152114

Hom.:

1375

Cov.:

show subpopulations

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.:

AF XY:

0.0714

AC XY:

5306

AN XY:

74286

show subpopulations

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:

AN:

656

European-Non Finnish (NFE)

AF:

0.0526

AC:

4788

AN:

91030

Other (OTH)

AF:

0.0709

AC:

648

AN:

9146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

452

904

1356

1808

2260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.112

AC:

17044

AN:

152232

Hom.:

1386

Cov.:

AF XY:

0.112

AC XY:

8349

AN XY:

74440

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3748

AN:

68030

Other (OTH)

AF:

0.105

AC:

221

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

732

1464

2196

2928

3660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.89

PhyloP100

3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over