chr16-30358009-G-C

Variant names:

• chr16-30358009-G-C
• rs1200891984
• NM_015527.4:c.2362C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015527.4(TBC1D10B):​c.2362C>G​(p.Pro788Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P788S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBC1D10B NM_015527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 0 publications found

Genes affected

TBC1D10B (HGNC:24510): (TBC1 domain family member 10B) Small G proteins of the RAB family (see MIM 179508) function in intracellular vesicle trafficking by switching from the GTP-bound state to the GDP-bound state with the assistance of guanine nucleotide exchange factors (GEFs; see MIM 609700) and GTPase-activating proteins (GAPs). TBC1D10B functions as a GAP for several proteins of the Rab family (Ishibashi et al., 2009 [PubMed 19077034]).[supplied by OMIM, Nov 2010]

CD2BP2-DT (HGNC:53029): (CD2BP2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03642544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBC1D10B	NM_015527.4	c.2362C>G	p.Pro788Ala	missense_variant	Exon 9 of 9	ENST00000409939.8	NP_056342.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBC1D10B	ENST00000409939.8	c.2362C>G	p.Pro788Ala	missense_variant	Exon 9 of 9	1	NM_015527.4	ENSP00000386538.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.17
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.062
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.11	T
Polyphen		0.043	B
Vest4		0.12
MutPred		0.14		Gain of MoRF binding (P = 0.0458);
MVP		0.068
MPC		0.12
ClinPred		0.044	T
GERP RS		0.51
Varity_R		0.037
gMVP		0.048

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1200891984; hg19: chr16-30369330;