rs1248236662

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-36166250-C-A
• chr17-36166250-C-G

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>T​(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. 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.

• Frequency:
  • Genomes: 𝑓 0.0000082 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3B NM_001001417.7 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.053554744).

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>T	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>T	p.Glu465Asp	missense	Exon 14 of 14	ENSP00000478473.1	A6NDS4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-10945C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000823 AC: 1 AN: 121458 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000252

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000167 AC: 2 AN: 1198924 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 598464

⚠️ 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: 33134

American (AMR) AF: 0.00 AC: 0 AN: 43078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00000225 AC: 2 AN: 890394

Other (OTH) AF: 0.00 AC: 0 AN: 51746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000823 AC: 1 AN: 121458 Hom.: 0 Cov.: 19 AF XY: 0.0000168 AC XY: 1 AN XY: 59526

African (AFR) AF: 0.0000252 AC: 1 AN: 39684

American (AMR) AF: 0.00 AC: 0 AN: 13022

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 3880

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46790

Other (OTH) AF: 0.00 AC: 0 AN: 1646

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

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	0.88
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.054	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

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;