rs13936

Variant names:

• chr5-179862659-G-A
• rs13936
• ENST00000518085.1:n.3245C>T

Variant summary

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

The ENST00000518085.1(TBC1D9B):​n.3245C>T variant causes a non coding transcript exon 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 ENST00000518085.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBC1D9B	NM_015043.4	c.*789C>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000355235.8	NP_055858.2
TBC1D9B	NM_198868.3	c.*789C>T		3_prime_UTR_variant	Exon 22 of 22		NP_942568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D9B	ENST00000355235.8	c.*789C>T		3_prime_UTR_variant	Exon 21 of 21	5	NM_015043.4	ENSP00000347375.3

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

African (AFR) AF: 0.0183 AC: 155 AN: 8468

American (AMR) AF: 0.350 AC: 9489 AN: 27114

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 934 AN: 10702

East Asian (EAS) AF: 0.354 AC: 3160 AN: 8922

South Asian (SAS) AF: 0.253 AC: 15084 AN: 59508

European-Finnish (FIN) AF: 0.158 AC: 2003 AN: 12696

Middle Eastern (MID) AF: 0.0935 AC: 257 AN: 2750

European-Non Finnish (NFE) AF: 0.0795 AC: 11916 AN: 149926

Other (OTH) AF: 0.118 AC: 1612 AN: 13674

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

African (AFR) AF: 0.0193 AC: 802 AN: 41564

American (AMR) AF: 0.199 AC: 3038 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1917 AN: 5174

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68018

Other (OTH) AF: 0.100 AC: 212 AN: 2110

Alfa AF: 0.0950 Hom.: 1299

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
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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