17-36171907-T-G

Variant names:

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

Variant summary

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

The NM_001001417.7(TBC1D3B):​c.445A>C​(p.Ile149Leu) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I149V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBC1D3B NM_001001417.7 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08581969).

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>C	p.Ile149Leu	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>C	p.Ile149Leu	missense	Exon 7 of 14	ENSP00000478473.1	A6NDS4
	TBC1D3B	ENST00000622280.1	TSL:5	n.417A>C		non_coding_transcript_exon	Exon 2 of 4
	ENSG00000276241	ENST00000617914.2	TSL:3	n.358-5288T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149244 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000242

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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1453750 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723436

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44666

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105292

Other (OTH) AF: 0.00 AC: 0 AN: 60108

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000670 AC: 1 AN: 149244 Hom.: 0 Cov.: 24 AF XY: 0.0000137 AC XY: 1 AN XY: 72808

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

African (AFR) AF: 0.0000242 AC: 1 AN: 41346

American (AMR) AF: 0.00 AC: 0 AN: 14936

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66146

Other (OTH) AF: 0.00 AC: 0 AN: 2036

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.77
DANN	Benign	0.85
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.15	N
PhyloP100		0.15
PrimateAI	Uncertain	0.74	T
Sift4G	Benign	0.074	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.56		Loss of glycosylation at S150 (P = 0.1124)
MVP		0.043
ClinPred		0.68	D
Varity_R		0.10
gMVP		0.056

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: rs201615087; hg19: chr17-34499266;