NM_001123391.4:c.440G>T

Variant names:

• chr17-38187891-C-A
• rs1288012542
• NM_001123391.4:c.440G>T

Variant summary

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

The NM_001123391.4(TBC1D3):​c.440G>T​(p.Arg147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 5/6 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. R147Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: TBC1D3 NM_001123391.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

TBC1D3 (HGNC:19031): (TBC1 domain family member 3) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

NPEPPSP1 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15326044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123391.4. 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
	TBC1D3	NM_001123391.4	MANE Select	c.440G>T	p.Arg147Leu	missense	Exon 7 of 14	NP_001116863.3	Q8IZP1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D3	ENST00000620215.3	TSL:1 MANE Select	c.440G>T	p.Arg147Leu	missense	Exon 7 of 14	ENSP00000478683.1	Q8IZP1-1
	TBC1D3	ENST00000896521.1		c.440G>T	p.Arg147Leu	missense	Exon 6 of 13	ENSP00000566580.1
	NPEPPSP1	ENST00000738688.1		n.412-33725G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00202 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.18
DEOGEN2	Benign	0.0067	T
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.15	T
PhyloP100		2.2
Sift4G	Benign	1.0	T
Vest4		0.16
gMVP		0.054

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1288012542; hg19: chr17-36288683;