Variant 13-75295271-A-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_014832.5(TBC1D4):c.3157-258T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,994 control chromosomes in the GnomAD database, including 26,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 26840 hom., cov: 32)

Consequence

TBC1D4
NM_014832.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.478

Variant links:

Genes affected

TBC1D4 (HGNC:19165): (TBC1 domain family member 4) This gene is a member of the Tre-2/BUB2/CDC16 domain family. The protein encoded by this gene is a Rab-GTPase-activating protein, and contains two phopshotyrosine-binding domains (PTB1 and PTB2), a calmodulin-binding domain (CBD), a Rab-GTPase domain, and multiple AKT phosphomotifs. This protein is thought to play an important role in glucose homeostasis by regulating the insulin-dependent trafficking of the glucose transporter 4 (GLUT4), important for removing glucose from the bloodstream into skeletal muscle and fat tissues. Reduced expression of this gene results in an increase in GLUT4 levels at the plasma membrane, suggesting that this protein is important in intracellular retention of GLUT4 under basal conditions. When exposed to insulin, this protein is phosphorylated, dissociates from GLUT4 vesicles, resulting in increased GLUT4 at the cell surface, and enhanced glucose transport. Phosphorylation of this protein by AKT is required for proper translocation of GLUT4 to the cell surface. Individuals homozygous for a mutation in this gene are at higher risk for type 2 diabetes and have higher levels of circulating glucose and insulin levels after glucose ingestion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

TBC1D4 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=-0.96).

BP6

Variant 13-75295271-A-T is Benign according to our data. Variant chr13-75295271-A-T is described in ClinVar as [Benign]. Clinvar id is 1236980.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D4	NM_014832.5 linkuse as main transcript	c.3157-258T>A		intron_variant		ENST00000377636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBC1D4	ENST00000377636.8 linkuse as main transcript	c.3157-258T>A		intron_variant		2	NM_014832.5	A1	O60343-1

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89106

AN:

151876

Hom.:

26814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.713

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.573

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

GnomAD4 genome

AF:

0.587

AC:

89184

AN:

151994

Hom.:

26840

Cov.:

AF XY:

0.580

AC XY:

43090

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.595

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.657

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.443

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.575

Alfa

AF:

0.487

Hom.:

1363

Bravo

AF:

0.582

Asia WGS

AF:

0.340

AC:

1183

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.23

DANN

Benign

0.44

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