NM_016495.6:c.406G>C

Variant names:

• chr6-13316684-C-G
• NM_016495.6:c.406G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016495.6(TBC1D7):​c.406G>C​(p.Ala136Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A136T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TBC1D7 NM_016495.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D7	NM_016495.6	c.406G>C	p.Ala136Pro	missense_variant	Exon 5 of 8	ENST00000379300.8	NP_057579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D7	ENST00000379300.8	c.406G>C	p.Ala136Pro	missense_variant	Exon 5 of 8	1	NM_016495.6	ENSP00000368602.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;T;T;.;T;.;.;.;.;.;.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D;D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L;L;L;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	.;N;N;N;.;N;N;N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.13	.;T;T;T;.;T;T;T;T;T;T;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;.;T;.;.;D
Polyphen		1.0	D;D;D;D;.;.;.;.;D;.;.;.
Vest4		0.91
MutPred		0.41		Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);.;.;.;.;Loss of helix (P = 0.0072);.;.;Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);
MVP		0.46
MPC		0.85
ClinPred		0.83	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: -7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-13316916;