Variant 2-101007870-A-AAAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

The NM_001330348.2(TBC1D8):c.3416_3418dupCTT(p.Thr1139_Phe1140insSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,864 control chromosomes in the GnomAD database, including 1,370 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.053 ( 715 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 655 hom. )

Consequence

TBC1D8
NM_001330348.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250

Variant links:

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]

TBC1D8 links:

RPL31 (HGNC:10334): (ribosomal protein L31) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001330348.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-101007870-A-AAAG is Benign according to our data. Variant chr2-101007870-A-AAAG is described in ClinVar as [Benign]. Clinvar id is 1248315.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2 link	c.3416_3418dupCTT	p.Thr1139_Phe1140insSer	conservative_inframe_insertion	20/20	ENST00000409318.2	NP_001317277.1	J3KQ40
TBC1D8	NM_001102426.3 link	c.3371_3373dupCTT	p.Thr1124_Phe1125insSer	conservative_inframe_insertion	20/20		NP_001095896.1	O95759-1
RPL31	NM_001098577.3 link	c.346+1800_346+1802dupAAG		intron_variant			NP_001092047.1	P62899-2
TBC1D8	NR_138475.2 link	n.3382_3384dupCTT		non_coding_transcript_exon_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2 link	c.3416_3418dupCTT	p.Thr1139_Phe1140insSer	conservative_inframe_insertion	20/20	5	NM_001330348.2	ENSP00000386856.1		J3KQ40

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8056

AN:

152056

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0138

AC:

3437

AN:

249220

Hom.:

287

AF XY:

0.0102

AC XY:

1382

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.00985

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000549

Gnomad OTH exome

AF:

0.00793

GnomAD4 exome

AF:

0.00571

AC:

8345

AN:

1461690

Hom.:

655

Cov.:

AF XY:

0.00496

AC XY:

3605

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000495

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0532

AC:

8090

AN:

152174

Hom.:

715

Cov.:

AF XY:

0.0521

AC XY:

3874

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0196

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.00908

Hom.:

Bravo

AF:

0.0609

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 32098966) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over