16-30358167-C-A

Variant names:

• chr16-30358167-C-A
• rs781225462
• NM_015527.4:c.2204G>T

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.2204G>T​(p.Arg735Leu) 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. R735Q) 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: 0.894
• Publications: 1 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=0.055086523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10B	NM_015527.4	MANE Select	c.2204G>T	p.Arg735Leu	missense	Exon 9 of 9	NP_056342.3
	CD2BP2-DT	NR_184230.1		n.1880C>A		non_coding_transcript_exon	Exon 2 of 2
	CD2BP2-DT	NR_184231.1		n.1953C>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D10B	ENST00000409939.8	TSL:1 MANE Select	c.2204G>T	p.Arg735Leu	missense	Exon 9 of 9	ENSP00000386538.3	Q4KMP7-1
	TBC1D10B	ENST00000955945.1		c.2243G>T	p.Arg748Leu	missense	Exon 9 of 9	ENSP00000626004.1
	TBC1D10B	ENST00000955946.1		c.2180G>T	p.Arg727Leu	missense	Exon 9 of 9	ENSP00000626005.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.055	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.1	L
PhyloP100		0.89
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.22
Sift	Benign	0.087	T
Sift4G	Benign	0.30	T
Polyphen		0.0070	B
Vest4		0.21
MutPred		0.25		Loss of solvent accessibility (P = 0.0299)
MVP		0.17
MPC		0.15
ClinPred		0.088	T
GERP RS		2.9
Varity_R		0.093
gMVP		0.086

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: rs781225462; hg19: chr16-30369488;