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GeneBe

4-6923644-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
TBC1D14NM_020773.3 linkuse as main transcriptc.255C>T p.His85= synonymous_variant 2/14 ENST00000409757.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBC1D14ENST00000409757.9 linkuse as main transcriptc.255C>T p.His85= synonymous_variant 2/141 NM_020773.3 Q9P2M4-1
TBC1D14ENST00000448507.5 linkuse as main transcriptc.255C>T p.His85= synonymous_variant 2/145 Q9P2M4-1
TBC1D14ENST00000444368.1 linkuse as main transcriptc.255C>T p.His85= synonymous_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0269
AC:
4090
AN:
152188
Hom.:
196
Cov.:
33
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.:
79
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0269
AC:
4094
AN:
152306
Hom.:
195
Cov.:
33
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.:
2
Bravo
AF:
0.0301
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000356

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 submitterclinical testingInvitaeAug 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.

Other links and lift over

dbSNP: rs34768850; hg19: chr4-6925371; API