6-13305113-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016495.6(TBC1D7):c.870C>G(p.Val290=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,864 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (74 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (61 hom.)
• Consequence: TBC1D7 NM_016495.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.28

Genes affected

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]

TBC1D7-LOC100130357 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-13305113-G-C is Benign according to our data. Variant chr6-13305113-G-C is described in ClinVar as [Benign]. Clinvar id is 778226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-13305113-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D7	NM_016495.6	c.870C>G	p.Val290=	synonymous_variant	8/8	ENST00000379300.8
TBC1D7-LOC100130357	NR_134872.2	n.610-10215C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D7	ENST00000379300.8	c.870C>G	p.Val290=	synonymous_variant	8/8	1	NM_016495.6	P1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2475 AN: 152176 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00467 AC: 1165 AN: 249458 Hom.: 18 AF XY: 0.00365 AC XY: 492 AN XY: 134790

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000622

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00212 AC: 3099 AN: 1460570 Hom.: 61 Cov.: 30 AF XY: 0.00190 AC XY: 1378 AN XY: 726604

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.00455

Gnomad4 ASJ exome AF: 0.0000768

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000460

Gnomad4 OTH exome AF: 0.00509

GnomAD4 genome AF: 0.0163 AC: 2480 AN: 152294 Hom.: 74 Cov.: 33 AF XY: 0.0161 AC XY: 1197 AN XY: 74470

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00527 Hom.: 2

Bravo AF: 0.0187

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000891

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 13, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.21
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs34295856; hg19: chr6-13305345;