14-45037654-G-T

Variant names:

• chr14-45037654-G-T
• rs2899961
• NM_001308120.2:c.3812+5278G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308120.2(TOGARAM1):​c.3812+5278G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,224 control chromosomes in the GnomAD database, including 155 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 0.027 (155 hom., cov: 32)
• Consequence: TOGARAM1 NM_001308120.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 2 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]

KLHL28 (HGNC:19741): (kelch like family member 28)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM1	NM_001308120.2	MANE Select	c.3812+5278G>T		intron	N/A	NP_001295049.1
	TOGARAM1	NM_015091.4		c.3812+5278G>T		intron	N/A	NP_055906.2
	TOGARAM1	NR_131765.2		n.3875+5278G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOGARAM1	ENST00000361462.7	TSL:1 MANE Select	c.3812+5278G>T		intron	N/A	ENSP00000354917.2
	TOGARAM1	ENST00000361577.7	TSL:1	c.3812+5278G>T		intron	N/A	ENSP00000355045.3
	TOGARAM1	ENST00000557423.5	TSL:1	n.*655+5278G>T		intron	N/A	ENSP00000451829.1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4088 AN: 152108 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0269 AC: 4096 AN: 152224 Hom.: 155 Cov.: 32 AF XY: 0.0280 AC XY: 2083 AN XY: 74430

African (AFR) AF: 0.00628 AC: 261 AN: 41542

American (AMR) AF: 0.107 AC: 1642 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0214 AC: 103 AN: 4824

European-Finnish (FIN) AF: 0.00604 AC: 64 AN: 10598

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0261 AC: 1775 AN: 68016

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0271 Hom.: 132

Bravo AF: 0.0324

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

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: rs2899961; hg19: chr14-45506857;