chr14-45037654-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOGARAM1	NM_001308120.2	c.3812+5278G>T		intron_variant	Intron 11 of 19	ENST00000361462.7	NP_001295049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOGARAM1	ENST00000361462.7	c.3812+5278G>T		intron_variant	Intron 11 of 19	1	NM_001308120.2	ENSP00000354917.2

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

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.00604

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0261 Hom.: 83

Bravo AF: 0.0324

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.69

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: rs2899961; hg19: chr14-45506857;