NM_001330348.2:c.631+1713C>T

Variant names:

• chr2-101052395-G-A
• rs2278729
• NM_001330348.2:c.631+1713C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330348.2(TBC1D8):​c.631+1713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,056 control chromosomes in the GnomAD database, including 5,569 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5569 hom., cov: 32)
• Consequence: TBC1D8 NM_001330348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 23 publications found

Genes affected

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330348.2. 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
	TBC1D8	NM_001330348.2	MANE Select	c.631+1713C>T		intron	N/A	NP_001317277.1	J3KQ40
	TBC1D8	NM_001102426.3		c.586+1713C>T		intron	N/A	NP_001095896.1	O95759-1
	TBC1D8	NR_138475.2		n.715+1713C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBC1D8	ENST00000409318.2	TSL:5 MANE Select	c.631+1713C>T		intron	N/A	ENSP00000386856.1	J3KQ40
	TBC1D8	ENST00000376840.8	TSL:1	c.586+1713C>T		intron	N/A	ENSP00000366036.4	O95759-1
	TBC1D8	ENST00000870702.1		c.631+1713C>T		intron	N/A	ENSP00000540761.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37435 AN: 151938 Hom.: 5571 Cov.: 32

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37434 AN: 152056 Hom.: 5569 Cov.: 32 AF XY: 0.244 AC XY: 18141 AN XY: 74288

African (AFR) AF: 0.0823 AC: 3415 AN: 41500

American (AMR) AF: 0.297 AC: 4540 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1493 AN: 3470

East Asian (EAS) AF: 0.0863 AC: 447 AN: 5178

South Asian (SAS) AF: 0.243 AC: 1172 AN: 4816

European-Finnish (FIN) AF: 0.277 AC: 2919 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22418 AN: 67976

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.296 Hom.: 14812

Bravo AF: 0.241

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.31
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2278729; hg19: chr2-101668857;