rs13936

Positions:

• chr5-179862659-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015043.4(TBC1D9B):​c.*789C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 446,016 control chromosomes in the GnomAD database, including 6,627 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 0.098 (1269 hom., cov: 33)
  • Exomes 𝑓: 0.15 (5358 hom.)
• Consequence: TBC1D9B NM_015043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

TBC1D9B (HGNC:29097): (TBC1 domain family member 9B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D9B	NM_015043.4	c.*789C>T		3_prime_UTR_variant	21/21	ENST00000355235.8
TBC1D9B	NM_198868.3	c.*789C>T		3_prime_UTR_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D9B	ENST00000355235.8	c.*789C>T		3_prime_UTR_variant	21/21	5	NM_015043.4	A2

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14901 AN: 152138 Hom.: 1264 Cov.: 33

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0924

GnomAD4 exome AF: 0.152 AC: 44610 AN: 293760 Hom.: 5358 Cov.: 0 AF XY: 0.159 AC XY: 26370 AN XY: 165496

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.0873

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.0795

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.0980 AC: 14914 AN: 152256 Hom.: 1269 Cov.: 33 AF XY: 0.108 AC XY: 8073 AN XY: 74434

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0991 Hom.: 872

Bravo AF: 0.0986

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13936; hg19: chr5-179289659; COSMIC: COSV52972891; COSMIC: COSV52972891;