17-38058219-A-G

Position:

• chr17-38058219-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001418.6(TBC1D3C):​c.1439T>C​(p.Val480Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3C NM_001001418.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.447

Genes affected

TBC1D3C (HGNC:24889): (TBC1 domain family member 3C) This gene represents one of a cluster of related genes found on chromosome 17. The proteins encoded by this gene family contain a TBC (Tre-2, Bub2p, and Cdc16p) domain and may be involved in GTPase signaling and vesicle trafficking. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081878304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D3C	NM_001001418.6	c.1439T>C	p.Val480Ala	missense_variant	14/14	ENST00000622206.2	NP_001001418.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D3C	ENST00000622206.2	c.1439T>C	p.Val480Ala	missense_variant	14/14	1	NM_001001418.6	ENSP00000482345	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4840 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.1439T>C (p.V480A) alteration is located in exon 14 (coding exon 13) of the TBC1D3C gene. This alteration results from a T to C substitution at nucleotide position 1439, causing the valine (V) at amino acid position 480 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0010	N
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
Sift4G	Benign	0.17	T
Vest4		0.11
MutPred		0.34		Loss of sheet (P = 0.0037);
MVP		0.014
ClinPred		0.43	T
GERP RS		0.12
Varity_R		0.077
gMVP		0.0053

Splicing

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: chr17-34746645;