NM_001001417.7:c.1395G>C

Variant names:

• chr17-36166250-C-G
• rs1248236662
• NM_001001417.7:c.1395G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001417.7(TBC1D3B):​c.1395G>C​(p.Glu465Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (4 hom., cov: 19)
  • Exomes 𝑓: 0.000059 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3B NM_001001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.05
• Publications: 0 publications found

Genes affected

TBC1D3B (HGNC:27011): (TBC1 domain family member 3B) This gene encodes a protein that is similar to TBC1 domain family, member 3. This protein contains a TBC (Tre-2, Bub2p, and Cdc16p) domain, which is found in proteins involved in RAB GTPase signaling and vesicle trafficking. There are multiple copies of this gene located within a cluster of chemokine genes on chromosome 17q. [provided by RefSeq, Apr 2009]

ENSG00000276241 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03831318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001417.7. 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
	TBC1D3B	NM_001001417.7	MANE Select	c.1395G>C	p.Glu465Asp	missense	Exon 14 of 14	NP_001001417.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D3B	ENST00000611257.5	TSL:1 MANE Select	c.1395G>C	p.Glu465Asp	missense	Exon 14 of 14	ENSP00000478473.1	A6NDS4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-10945C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 59 AN: 121438 Hom.: 4 Cov.: 19

Gnomad AFR AF: 0.00144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000154

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000592 AC: 71 AN: 1198908 Hom.: 9 Cov.: 32 AF XY: 0.0000568 AC XY: 34 AN XY: 598460

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00130 AC: 43 AN: 33120

American (AMR) AF: 0.000116 AC: 5 AN: 43078

Ashkenazi Jewish (ASJ) AF: 0.000401 AC: 9 AN: 22426

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 80066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3788

European-Non Finnish (NFE) AF: 0.0000101 AC: 9 AN: 890394

Other (OTH) AF: 0.0000966 AC: 5 AN: 51744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000489701), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000485 AC: 59 AN: 121558 Hom.: 4 Cov.: 19 AF XY: 0.000453 AC XY: 27 AN XY: 59646

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00143 AC: 57 AN: 39788

American (AMR) AF: 0.000153 AC: 2 AN: 13040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2616

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 3874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46784

Other (OTH) AF: 0.00 AC: 0 AN: 1668

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000911844), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.021	D
Polyphen		0.030	B
Vest4		0.070
MutPred		0.26		Loss of catalytic residue at E465 (P = 0.0295)
MVP		0.043
ClinPred		0.068	T
Varity_R		0.12
gMVP		0.011
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1248236662; hg19: chr17-34493630;