Variant chr4-6923644-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020773.3(TBC1D14):c.255C>T(p.His85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,613,902 control chromosomes in the GnomAD database, including 384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 195 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 189 hom. )

Consequence

TBC1D14
NM_020773.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

TBC1D14 (HGNC:29246): (TBC1 domain family member 14) Enables protein kinase binding activity. Involved in negative regulation of autophagy; recycling endosome to Golgi transport; and regulation of autophagosome assembly. Located in several cellular components, including Golgi apparatus; autophagosome; and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-6923644-C-T is Benign according to our data. Variant chr4-6923644-C-T is described in ClinVar as [Benign]. Clinvar id is 791969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBC1D14	NM_020773.3 linkuse as main transcript	c.255C>T	p.His85=	synonymous_variant	2/14	ENST00000409757.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
TBC1D14	ENST00000409757.9 linkuse as main transcript	c.255C>T	p.His85=	synonymous_variant	2/14	1	NM_020773.3	Q9P2M4-1
TBC1D14	ENST00000448507.5 linkuse as main transcript	c.255C>T	p.His85=	synonymous_variant	2/14	5		Q9P2M4-1
TBC1D14	ENST00000444368.1 linkuse as main transcript	c.255C>T	p.His85=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4090

AN:

152188

Hom.:

196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0938

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.00715

AC:

1794

AN:

251032

Hom.:

AF XY:

0.00552

AC XY:

750

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0956

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00477

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00284

AC:

4152

AN:

1461596

Hom.:

189

Cov.:

AF XY:

0.00249

AC XY:

1811

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0969

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.00589

GnomAD4 genome

AF:

0.0269

AC:

4094

AN:

152306

Hom.:

195

Cov.:

AF XY:

0.0252

AC XY:

1876

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0936

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.38

DANN

Benign

0.65

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