Variant 2-101019076-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001330348.2(TBC1D8):c.2827+2605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,592,348 control chromosomes in the GnomAD database, including 72,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 5376 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66967 hom. )

Consequence

TBC1D8
NM_001330348.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 2-101019076-C-T is Benign according to our data. Variant chr2-101019076-C-T is described in ClinVar as [Benign]. Clinvar id is 1287016.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
TBC1D8	NM_001330348.2 linkuse as main transcript	c.2827+2605G>A	intron_variant		ENST00000409318.2
RPL31	NM_001098577.3 linkuse as main transcript	c.*38C>T	3_prime_UTR_variant	5/5
TBC1D8	NM_001102426.3 linkuse as main transcript	c.2782+2605G>A	intron_variant
TBC1D8	NR_138475.2 linkuse as main transcript	n.2793+2605G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D8	ENST00000409318.2 linkuse as main transcript	c.2827+2605G>A		intron_variant		5	NM_001330348.2	A1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37139

AN:

151926

Hom.:

5375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.269

GnomAD3 exomes

AF:

0.280

AC:

60603

AN:

216330

Hom.:

9049

AF XY:

0.288

AC XY:

33468

AN XY:

116246

show subpopulations

Gnomad AFR exome

AF:

0.0815

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.299

AC:

430852

AN:

1440304

Hom.:

66967

Cov.:

AF XY:

0.302

AC XY:

215954

AN XY:

714224

show subpopulations

Gnomad4 AFR exome

AF:

0.0834

Gnomad4 AMR exome

AF:

0.265

Gnomad4 ASJ exome

AF:

0.446

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.244

AC:

37142

AN:

152044

Hom.:

5376

Cov.:

AF XY:

0.245

AC XY:

18218

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0906

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.298

Hom.:

3483

Bravo

AF:

0.236

Asia WGS

AF:

0.264

AC:

917

AN:

3478

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

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

Cadd

Benign

1.3

Dann

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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