17-36171907-T-C

Variant names:

• chr17-36171907-T-C
• rs201615087
• NM_001001417.7:c.445A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001001417.7(TBC1D3B):​c.445A>G​(p.Ile149Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 149,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000064 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3B NM_001001417.7 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.150
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051583827).
• BP6: Variant 17-36171907-T-C is Benign according to our data. Variant chr17-36171907-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2345611.Status of the report is criteria_provided_single_submitter, 1 stars.

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.445A>G	p.Ile149Val	missense	Exon 7 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.445A>G	p.Ile149Val	missense	Exon 7 of 14	ENSP00000478473.1	A6NDS4
	TBC1D3B	ENST00000622280.1	TSL:5	n.417A>G		non_coding_transcript_exon	Exon 2 of 4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-5288T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 20 AN: 149176 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000469

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: 0.0000756

Gnomad OTH AF: 0.00246

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000640 AC: 93 AN: 1453672 Hom.: 6 Cov.: 33 AF XY: 0.0000802 AC XY: 58 AN XY: 723392

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

African (AFR) AF: 0.0000300 AC: 1 AN: 33378

American (AMR) AF: 0.000134 AC: 6 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5230

European-Non Finnish (NFE) AF: 0.0000679 AC: 75 AN: 1105274

Other (OTH) AF: 0.0000166 AC: 1 AN: 60092

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000134 AC: 20 AN: 149292 Hom.: 0 Cov.: 24 AF XY: 0.000110 AC XY: 8 AN XY: 72906

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

African (AFR) AF: 0.0000724 AC: 3 AN: 41432

American (AMR) AF: 0.000468 AC: 7 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000756 AC: 5 AN: 66128

Other (OTH) AF: 0.00243 AC: 5 AN: 2058

⚠️ 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: Likely benign

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	0.092
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.017
DANN	Benign	0.17
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N
PhyloP100		0.15
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.082
MutPred		0.39		Loss of disorder (P = 0.2077)
MVP		0.043
ClinPred		0.039	T
Varity_R		0.054
gMVP		0.021
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs201615087; hg19: chr17-34499266;