2-101011463-C-T

Position:

chr2-101011463-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330348.2(TBC1D8):c.2905G>A(p.Gly969Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,398 control chromosomes in the GnomAD database, including 13,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 869 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12477 hom. )

Consequence

TBC1D8
NM_001330348.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.02

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014540851).

BP6

Variant 2-101011463-C-T is Benign according to our data. Variant chr2-101011463-C-T is described in ClinVar as [Benign]. Clinvar id is 1256912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D8	NM_001330348.2 link	c.2905G>A	p.Gly969Arg	missense_variant	18/20	ENST00000409318.2	NP_001317277.1	J3KQ40
TBC1D8	NM_001102426.3 link	c.2860G>A	p.Gly954Arg	missense_variant	18/20		NP_001095896.1	O95759-1
RPL31	NM_001098577.3 link	c.346+5392C>T		intron_variant			NP_001092047.1	P62899-2
TBC1D8	NR_138475.2 link	n.2871G>A		non_coding_transcript_exon_variant	17/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D8	ENST00000409318.2 link	c.2905G>A	p.Gly969Arg	missense_variant	18/20	5	NM_001330348.2	ENSP00000386856.1		J3KQ40

Frequencies

GnomAD3 genomes

AF:

0.0920

AC:

13972

AN:

151810

Hom.:

869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0939

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0997

GnomAD3 exomes

AF:

0.0978

AC:

24376

AN:

249208

Hom.:

1597

AF XY:

0.100

AC XY:

13513

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.0627

Gnomad ASJ exome

AF:

0.0580

Gnomad EAS exome

AF:

0.000389

Gnomad SAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.123

AC:

179841

AN:

1461470

Hom.:

12477

Cov.:

AF XY:

0.121

AC XY:

88184

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.0658

Gnomad4 ASJ exome

AF:

0.0565

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.0644

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0920

AC:

13970

AN:

151928

Hom.:

869

Cov.:

AF XY:

0.0923

AC XY:

6848

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.0937

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0593

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.0987

Alfa

AF:

0.119

Hom.:

2523

Bravo

AF:

0.0850

TwinsUK

AF:

0.144

AC:

534

ALSPAC

AF:

0.143

AC:

552

ESP6500AA

AF:

0.0262

AC:

101

ESP6500EA

AF:

0.130

AC:

1073

ExAC

AF:

0.0984

AC:

11890

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2019	This variant is associated with the following publications: (PMID: 29083408) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.13

Sift

Benign

0.069

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.015

B;.

Vest4

0.16

MutPred

0.26

Gain of loop (P = 0.0097);.;

MPC

0.45

ClinPred

0.028

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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