17-38059672-G-A

Position:

• chr17-38059672-G-A

Variant summary

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

The NM_001001418.6(TBC1D3C):​c.967C>T​(p.Arg323Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 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)
• Consequence: TBC1D3C NM_001001418.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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=0.10074872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D3C	NM_001001418.6	c.967C>T	p.Arg323Cys	missense_variant	13/14	ENST00000622206.2	NP_001001418.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D3C	ENST00000622206.2	c.967C>T	p.Arg323Cys	missense_variant	13/14	1	NM_001001418.6	ENSP00000482345	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

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

Jul 06, 2021

The c.967C>T (p.R323C) alteration is located in exon 13 (coding exon 12) of the TBC1D3C gene. This alteration results from a C to T substitution at nucleotide position 967, causing the arginine (R) at amino acid position 323 to be replaced by a cysteine (C). 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	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0014	N
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.96	D;D;D;D;D;N;N;N;N
Sift4G	Benign	0.18	T
Vest4		0.12
MVP		0.040
ClinPred		0.52	D
GERP RS		-0.70
Varity_R		0.098
gMVP		0.042

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: chr17-34748080;