rs3759171

Variant names:

• chr12-71913836-A-G
• rs3759171
• NM_001146213.3:c.1311A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-71913836-A-G
• chr12-71913836-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001146213.3(TBC1D15):​c.1311A>G​(p.Gln437Gln) 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146213.3. 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
	TBC1D15	NM_001146213.3	MANE Select	c.1311A>G	p.Gln437Gln	synonymous	Exon 12 of 17	NP_001139685.2
	TBC1D15	NM_022771.6		c.1362A>G	p.Gln454Gln	synonymous	Exon 13 of 18	NP_073608.4
	TBC1D15	NM_001385848.1		c.1311A>G	p.Gln437Gln	synonymous	Exon 12 of 17	NP_001372777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D15	ENST00000485960.7	TSL:1 MANE Select	c.1311A>G	p.Gln437Gln	synonymous	Exon 12 of 17	ENSP00000420678.2
	TBC1D15	ENST00000550746.5	TSL:1	c.1362A>G	p.Gln454Gln	synonymous	Exon 13 of 18	ENSP00000448182.1
	TBC1D15	ENST00000462788.6	TSL:1	n.*725A>G		non_coding_transcript_exon	Exon 11 of 16	ENSP00000418467.2

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

GnomAD2 exomes AF: 0.436 AC: 91331 AN: 209374 AF XY: 0.418

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 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

African (AFR) AF: 0.881 AC: 26089 AN: 29598

American (AMR) AF: 0.634 AC: 21296 AN: 33610

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 6727 AN: 24828

East Asian (EAS) AF: 0.910 AC: 33699 AN: 37016

South Asian (SAS) AF: 0.532 AC: 41865 AN: 78752

European-Finnish (FIN) AF: 0.318 AC: 16808 AN: 52808

Middle Eastern (MID) AF: 0.336 AC: 1891 AN: 5626

European-Non Finnish (NFE) AF: 0.281 AC: 307359 AN: 1091936

Other (OTH) AF: 0.380 AC: 22185 AN: 58320

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

African (AFR) AF: 0.866 AC: 35922 AN: 41494

American (AMR) AF: 0.538 AC: 8193 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 949 AN: 3466

East Asian (EAS) AF: 0.893 AC: 4621 AN: 5174

South Asian (SAS) AF: 0.552 AC: 2662 AN: 4826

European-Finnish (FIN) AF: 0.320 AC: 3375 AN: 10556

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19341 AN: 67782

Other (OTH) AF: 0.463 AC: 977 AN: 2108

Alfa AF: 0.357 Hom.: 49364

Bravo AF: 0.536

Asia WGS AF: 0.717 AC: 2484 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.7
DANN	Benign	0.44
PhyloP100		2.7
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3759171; hg19: chr12-72307616; COSMIC: COSV59853499;