8-123072785-C-G

Position:

• chr8-123072785-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145647.4(TBC1D31):​c.16C>G​(p.Leu6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBC1D31 NM_145647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.534

Genes affected

TBC1D31 (HGNC:30888): (TBC1 domain family member 31) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08969456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D31	NM_145647.4	c.16C>G	p.Leu6Val	missense_variant	1/22	ENST00000287380.6	NP_663622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D31	ENST00000287380.6	c.16C>G	p.Leu6Val	missense_variant	1/22	1	NM_145647.4	ENSP00000287380	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 06, 2021

The c.16C>G (p.L6V) alteration is located in exon 1 (coding exon 1) of the TBC1D31 gene. This alteration results from a C to G substitution at nucleotide position 16, causing the leucine (L) at amino acid position 6 to be replaced by a valine (V). 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
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0021	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N;N
MutationTaster	Benign	0.94	D;D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.012
Sift	Benign	0.31	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.68	P;.
Vest4		0.18
MutPred		0.36		Gain of MoRF binding (P = 0.0772);Gain of MoRF binding (P = 0.0772);
MVP		0.64
MPC		0.081
ClinPred		0.26	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.079
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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: chr8-124085025;