16-30358040-CC-TT

Variant names:

• chr16-30358040-CC-TT
• NM_015527.4:c.2330_2331delGGinsAA
• TBC1D10B p.Arg777Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015527.4(TBC1D10B):​c.2330_2331delGGinsAA​(p.Arg777Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R777W) 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: 1.92
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.2330_2331delGGinsAA	p.Arg777Gln	missense	N/A	NP_056342.3
	CD2BP2-DT	NR_184230.1		n.1753_1754delCCinsTT		non_coding_transcript_exon	Exon 2 of 2
	CD2BP2-DT	NR_184231.1		n.1826_1827delCCinsTT		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.2330_2331delGGinsAA	p.Arg777Gln	missense	N/A	ENSP00000386538.3	Q4KMP7-1
	TBC1D10B	ENST00000955945.1		c.2369_2370delGGinsAA	p.Arg790Gln	missense	N/A	ENSP00000626004.1
	TBC1D10B	ENST00000955946.1		c.2306_2307delGGinsAA	p.Arg769Gln	missense	N/A	ENSP00000626005.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-30369361;