rs10896172

Positions:

• chr11-67408221-T-C

Variant summary

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

The NM_001369496.1(TBC1D10C):​c.839-758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,372 control chromosomes in the GnomAD database, including 546 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 0.077 (546 hom., cov: 33)
  • Exomes 𝑓: 0.058 (0 hom.)
• Consequence: TBC1D10C NM_001369496.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

Genes affected

TBC1D10C (HGNC:24702): (TBC1 domain family member 10C) The protein encoded by this gene has an N-terminal Rab-GTPase domain and a binding site at the C-terminus for calcineurin, and is an inhibitor of both the Ras signaling pathway and calcineurin, a phosphatase regulated by calcium and calmodulin. Genes encoding similar proteins are located on chromosomes 16 and 22. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D10C	NM_001369496.1	c.839-758T>C		intron_variant		ENST00000542590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D10C	ENST00000542590.2	c.839-758T>C		intron_variant		1	NM_001369496.1	P1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11678 AN: 152202 Hom.: 545 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0655

GnomAD4 exome AF: 0.0577 AC: 3 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 2 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0768 AC: 11692 AN: 152320 Hom.: 546 Cov.: 33 AF XY: 0.0747 AC XY: 5567 AN XY: 74484

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0601 Hom.: 416

Bravo AF: 0.0830

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.79

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: rs10896172; hg19: chr11-67175692;