rs3759171

chr12-71913836-A-Gchr12-71913836-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001146213.3(TBC1D15):c.1311A>G(p.Gln437=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,564,336 control chromosomes in the GnomAD database, including 122,381 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 0.50 (24503 hom., cov: 32)
  • Exomes 𝑓: 0.34 (97878 hom.)
• Consequence: TBC1D15 NM_001146213.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

Genes affected

TBC1D15 (HGNC:25694): (TBC1 domain family member 15) This gene encodes a member of the Ras-like proteins in brain-GTPase activating protein superfamily that share a conserved Tre-2/Bub2/Cdc16 domain. The encoded protein interacts with Ras-like protein in brain 5A and may function as a regulator of intracellular trafficking. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=2.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D15	NM_001146213.3	c.1311A>G	p.Gln437=	synonymous_variant	12/17	ENST00000485960.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D15	ENST00000485960.7	c.1311A>G	p.Gln437=	synonymous_variant	12/17	1	NM_001146213.3	P3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76201 AN: 151724 Hom.: 24428 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.458

GnomAD3 exomes AF: 0.436 AC: 91331 AN: 209374 Hom.: 25311 AF XY: 0.418 AC XY: 47848 AN XY: 114486

Gnomad AFR exome AF: 0.876

Gnomad AMR exome AF: 0.656

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.900

Gnomad SAS exome AF: 0.532

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.338 AC: 477919 AN: 1412494 Hom.: 97878 Cov.: 29 AF XY: 0.341 AC XY: 239793 AN XY: 702844

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.910

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.380

GnomAD4 genome AF: 0.503 AC: 76335 AN: 151842 Hom.: 24503 Cov.: 32 AF XY: 0.509 AC XY: 37780 AN XY: 74216

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.463

Alfa AF: 0.325 Hom.: 19765

Bravo AF: 0.536

Asia WGS AF: 0.717 AC: 2484 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.7
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3759171; hg19: chr12-72307616; COSMIC: COSV59853499;