6-13294772-C-T

Position:

• chr6-13294772-C-T

Variant summary

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

The NM_001318809.2(TBC1D7-LOC100130357):​c.*39+10290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,242,554 control chromosomes in the GnomAD database, including 23,802 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 0.17 (2245 hom., cov: 33)
  • Exomes 𝑓: 0.19 (21557 hom.)
• Consequence: TBC1D7-LOC100130357 NM_001318809.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

TBC1D7-LOC100130357 (HGNC:):

TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D7-LOC100130357	NM_001318809.2	c.*39+10290G>A		intron_variant			NP_001305738.1
TBC1D7-LOC100130357	NR_134872.2	n.712+24G>A		intron_variant
LOC100130357	NR_160971.1	n.318+24G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000606214.5	c.*39+10290G>A		intron_variant		5		ENSP00000475727.1
TBC1D7	ENST00000421203.6	n.*82+24G>A		intron_variant		2		ENSP00000401438.2
ENSG00000215022	ENST00000606150.5	n.318+24G>A		intron_variant		2
ENSG00000215022	ENST00000612479.1	n.140+24G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25491 AN: 152122 Hom.: 2250 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

GnomAD3 exomes AF: 0.200 AC: 27715 AN: 138912 Hom.: 3027 AF XY: 0.208 AC XY: 15588 AN XY: 74940

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.270

Gnomad SAS exome AF: 0.296

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.194 AC: 211373 AN: 1090312 Hom.: 21557 Cov.: 17 AF XY: 0.197 AC XY: 106075 AN XY: 537356

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.167 AC: 25491 AN: 152242 Hom.: 2245 Cov.: 33 AF XY: 0.169 AC XY: 12578 AN XY: 74436

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.161

Alfa AF: 0.173 Hom.: 508

Bravo AF: 0.160

Asia WGS AF: 0.289 AC: 1003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs20499; hg19: chr6-13295004; COSMIC: COSV69720961; COSMIC: COSV69720961;