11-67405100-T-C

Variant names:

• chr11-67405100-T-C
• rs142040344
• NM_001369496.1:c.168T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001369496.1(TBC1D10C):​c.168T>C​(p.Pro56Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,551,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (0 hom.)
• Consequence: TBC1D10C NM_001369496.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.978
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-67405100-T-C is Benign according to our data. Variant chr11-67405100-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2642014.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.978 with no splicing effect.

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.168T>C	p.Pro56Pro	synonymous	Exon 2 of 9	NP_001356425.1	Q8IV04-1
	TBC1D10C	NM_001369498.1		c.168T>C	p.Pro56Pro	synonymous	Exon 2 of 9	NP_001356427.1
	TBC1D10C	NM_001369497.1		c.168T>C	p.Pro56Pro	synonymous	Exon 3 of 10	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.168T>C	p.Pro56Pro	synonymous	Exon 2 of 9	ENSP00000443654.1	Q8IV04-1
	TBC1D10C	ENST00000946012.1		c.168T>C	p.Pro56Pro	synonymous	Exon 2 of 9	ENSP00000616071.1
	TBC1D10C	ENST00000868931.1		c.168T>C	p.Pro56Pro	synonymous	Exon 3 of 10	ENSP00000538990.1

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152188 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000512 AC: 80 AN: 156246 AF XY: 0.000474

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.000353

Gnomad EAS exome AF: 0.0000883

Gnomad FIN exome AF: 0.000392

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.000483 AC: 675 AN: 1398870 Hom.: 0 Cov.: 31 AF XY: 0.000536 AC XY: 370 AN XY: 689936

African (AFR) AF: 0.0000633 AC: 2 AN: 31596

American (AMR) AF: 0.000252 AC: 9 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25168

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.0000884 AC: 7 AN: 79228

European-Finnish (FIN) AF: 0.000613 AC: 30 AN: 48944

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5636

European-Non Finnish (NFE) AF: 0.000551 AC: 594 AN: 1078878

Other (OTH) AF: 0.000397 AC: 23 AN: 57982

GnomAD4 genome AF: 0.000643 AC: 98 AN: 152306 Hom.: 1 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000588 AC: 9 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68006

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000962 Hom.: 0

Bravo AF: 0.000446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.5
DANN	Benign	0.66
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs142040344; hg19: chr11-67172571;