chr11-67408221-T-C

Variant names:

• chr11-67408221-T-C
• rs10896172
• NM_001369496.1:c.839-758T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369496.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10C	NM_001369496.1	MANE Select	c.839-758T>C		intron	N/A	NP_001356425.1	Q8IV04-1
	TBC1D10C	NM_001369498.1		c.863-758T>C		intron	N/A	NP_001356427.1
	TBC1D10C	NM_001369497.1		c.839-758T>C		intron	N/A	NP_001356426.1	Q8IV04-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10C	ENST00000542590.2	TSL:1 MANE Select	c.839-758T>C		intron	N/A	ENSP00000443654.1	Q8IV04-1
	TBC1D10C	ENST00000946012.1		c.863-758T>C		intron	N/A	ENSP00000616071.1
	TBC1D10C	ENST00000868931.1		c.839-758T>C		intron	N/A	ENSP00000538990.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.107 AC: 3 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.124 AC: 5166 AN: 41556

American (AMR) AF: 0.0488 AC: 747 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.162 AC: 839 AN: 5186

South Asian (SAS) AF: 0.0364 AC: 176 AN: 4832

European-Finnish (FIN) AF: 0.0522 AC: 555 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0571 AC: 3882 AN: 68022

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0618 Hom.: 558

Bravo AF: 0.0830

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.79
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10896172; hg19: chr11-67175692;