chr17-38066808-C-T

Variant names:

• chr17-38066808-C-T
• NM_001001418.6:c.97G>A

Variant summary

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

The NM_001001418.6(TBC1D3C):​c.97G>A​(p.Asp33Asn) 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)
• Consequence: TBC1D3C NM_001001418.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

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=0.1376887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D3C	NM_001001418.6	c.97G>A	p.Asp33Asn	missense_variant	Exon 3 of 14	ENST00000622206.2	NP_001001418.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D3C	ENST00000622206.2	c.97G>A	p.Asp33Asn	missense_variant	Exon 3 of 14	1	NM_001001418.6	ENSP00000482345.1

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

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97G>A (p.D33N) alteration is located in exon 3 (coding exon 2) of the TBC1D3C gene. This alteration results from a G to A substitution at nucleotide position 97, causing the aspartic acid (D) at amino acid position 33 to be replaced by an asparagine (N). 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	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.0084	N
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.90	T
Sift4G	Uncertain	0.051	T
Vest4		0.11
MutPred		0.37		Loss of ubiquitination at K34 (P = 0.0262);
MVP		0.048
ClinPred		0.50	D
GERP RS		0.47
Varity_R		0.067
gMVP		0.014

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: chr17-34755207;