chr6-13294772-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001318809.2(TBC1D7-LOC100130357):​c.*39+10290G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

TBC1D7-LOC100130357
NM_001318809.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

9 publications found
Variant links:
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 Gene-Disease associations (from GenCC):
  • macrocephaly/megalencephaly syndrome, autosomal recessive
    Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D7-LOC100130357NM_001318809.2 linkc.*39+10290G>T intron_variant Intron 8 of 8 NP_001305738.1 Q9P0N9-1A0A024QZX0
TBC1D7-LOC100130357NR_134872.2 linkn.712+24G>T intron_variant Intron 6 of 7
LOC100130357NR_160971.1 linkn.318+24G>T intron_variant Intron 3 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D7ENST00000606214.5 linkc.*39+10290G>T intron_variant Intron 7 of 7 5 ENSP00000475727.1 Q9P0N9-1
TBC1D7ENST00000421203.6 linkn.*82+24G>T intron_variant Intron 6 of 7 2 ENSP00000401438.2 B4DK47
ENSG00000215022ENST00000606150.5 linkn.318+24G>T intron_variant Intron 3 of 4 2
ENSG00000215022ENST00000612479.1 linkn.140+24G>T intron_variant Intron 2 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
17
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.12
DANN
Benign
0.70
PhyloP100
-1.3
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

Other links and lift over

dbSNP: rs20499; hg19: chr6-13295004; API