17-36260240-C-T

Position:

• chr17-36260240-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001291463.2(TBC1D3I):​c.376G>A​(p.Gly126Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3I NM_001291463.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.37

Genes affected

TBC1D3I (HGNC:32709): (TBC1 domain family member 3I) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026156902).
• BP6: Variant 17-36260240-C-T is Benign according to our data. Variant chr17-36260240-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3026214.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D3I	NM_001291463.2	c.376G>A	p.Gly126Arg	missense_variant	6/14	ENST00000621034.2	NP_001278392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D3I	ENST00000621034.2	c.376G>A	p.Gly126Arg	missense_variant	6/14	1	NM_001291463.2	ENSP00000481258	P1
TBC1D3I	ENST00000618620.4	c.376G>A	p.Gly126Arg	missense_variant	6/12	1		ENSP00000479474
TBC1D3I	ENST00000616671.4	c.376G>A	p.Gly126Arg	missense_variant	5/11	5		ENSP00000482914

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00125 AC: 24 AN: 19270 Hom.: 3 AF XY: 0.000627 AC XY: 6 AN XY: 9576

Gnomad AFR exome AF: 0.000343

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00142

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000295 AC: 1 AN: 339388 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 169526

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: 0.00000449

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ExAC AF: 0.543 AC: 1229

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

TBC1D3C: BS2; TBC1D3I: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.1
DANN	Benign	0.67
DEOGEN2	Benign	0.050	.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.91	N;N;N;N;D;D
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.29	T;T;T
Vest4		0.048
ClinPred		0.0066	T
GERP RS		-0.093
Varity_R		0.081
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1597756093; hg19: chr17-34587708;