17-36166449-C-T

Variant names:

• chr17-36166449-C-T
• rs1180655841
• NM_001001417.7:c.1196G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001417.7(TBC1D3B):​c.1196G>A​(p.Arg399Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3B NM_001001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.544
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07082906).

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.1196G>A	p.Arg399Gln	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.1196G>A	p.Arg399Gln	missense	Exon 14 of 14	ENSP00000478473.1	A6NDS4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-10746C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 4 AN: 39684 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000253

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000469 AC: 31 AN: 660804 Hom.: 0 Cov.: 8 AF XY: 0.0000449 AC XY: 15 AN XY: 333944

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

African (AFR) AF: 0.00 AC: 0 AN: 21010

American (AMR) AF: 0.0000631 AC: 2 AN: 31702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12992

East Asian (EAS) AF: 0.00 AC: 0 AN: 34848

South Asian (SAS) AF: 0.0000364 AC: 2 AN: 54892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2362

European-Non Finnish (NFE) AF: 0.0000536 AC: 24 AN: 448072

Other (OTH) AF: 0.0000959 AC: 3 AN: 31276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000144329), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000101 AC: 4 AN: 39684 Hom.: 0 Cov.: 5 AF XY: 0.0000522 AC XY: 1 AN XY: 19174

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

African (AFR) AF: 0.00 AC: 0 AN: 9866

American (AMR) AF: 0.00 AC: 0 AN: 6588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 776

East Asian (EAS) AF: 0.00 AC: 0 AN: 2768

South Asian (SAS) AF: 0.00 AC: 0 AN: 1006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 52

European-Non Finnish (NFE) AF: 0.000253 AC: 4 AN: 15808

Other (OTH) AF: 0.00 AC: 0 AN: 482

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), 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	0.082
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.1
DANN	Benign	0.97
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.54
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.43	T
Polyphen		0.0010	B
Vest4		0.095
MutPred		0.22		Loss of MoRF binding (P = 0.0344)
MVP		0.043
ClinPred		0.23	T
Varity_R		0.043
gMVP		0.027
Mutation Taster		=100/0	polymorphism

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: rs1180655841; hg19: chr17-34493829;