Variant 4-6923531-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020773.3(TBC1D14):c.142C>T(p.Pro48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TBC1D14
NM_020773.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14103723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D14	NM_020773.3 link	c.142C>T	p.Pro48Ser	missense_variant	2/14	ENST00000409757.9	NP_065824.2	Q9P2M4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBC1D14	ENST00000409757.9 link	c.142C>T	p.Pro48Ser	missense_variant	2/14	1	NM_020773.3	ENSP00000386921.4	Q9P2M4-1
TBC1D14	ENST00000448507.5 link	c.142C>T	p.Pro48Ser	missense_variant	2/14	5		ENSP00000404041.1	Q9P2M4-1
TBC1D14	ENST00000444368.1 link	c.142C>T	p.Pro48Ser	missense_variant	2/2	3		ENSP00000414951.1	C9JP26
TBC1D14	ENST00000427736.1 link	c.142C>T	p.Pro48Ser	missense_variant	2/2	2		ENSP00000411760.1	C9J541

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2024

The c.142C>T (p.P48S) alteration is located in exon 2 (coding exon 1) of the TBC1D14 gene. This alteration results from a C to T substitution at nucleotide position 142, causing the proline (P) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

T;T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.3

.;L;L;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.6

D;N;N;D

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.0030

.;B;B;.

Vest4

0.21, 0.21

MutPred

0.26

Gain of phosphorylation at P48 (P = 0.0351);Gain of phosphorylation at P48 (P = 0.0351);Gain of phosphorylation at P48 (P = 0.0351);Gain of phosphorylation at P48 (P = 0.0351);

MVP

0.33

MPC

0.30

ClinPred

0.66

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over