Variant 6-41691063-G-A 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_001271944.2(TFEB):c.151C>T(p.Pro51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,419,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TFEB
NM_001271944.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.81

Variant links:

Genes affected

TFEB (HGNC:11753): (transcription factor EB) Enables DNA-binding transcription factor activity; enzyme binding activity; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular response to amino acid starvation; lysosome localization; and positive regulation of autophagy. Located in cytosol; lysosomal membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TFEB 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=0.22918645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFEB	NM_001271944.2 linkuse as main transcript	c.151C>T	p.Pro51Ser	missense_variant	2/9	ENST00000373033.6	NP_001258873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFEB	ENST00000373033.6 linkuse as main transcript	c.151C>T	p.Pro51Ser	missense_variant	2/9	1	NM_001271944.2	ENSP00000362124	P1	P19484-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1419880

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Feb 02, 2024

The c.151C>T (p.P51S) alteration is located in exon 3 (coding exon 1) of the TFEB gene. This alteration results from a C to T substitution at nucleotide position 151, causing the proline (P) at amino acid position 51 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

0.23

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;D;T;D;.;D;.;T;.;.;.;T

Eigen

Benign

0.039

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;.;D;D;D;.;D;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;L;.;L;L;L;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.0

D;D;D;D;N;D;D;D;D;D;D;D

REVEL

Benign

0.090

Sift

Benign

0.11

T;D;D;D;T;D;T;T;T;T;D;D

Sift4G

Benign

0.14

T;T;T;T;T;T;T;.;.;.;D;D

Polyphen

0.21

B;B;B;B;P;B;.;.;.;.;.;.

Vest4

0.37

MutPred

0.24

Gain of phosphorylation at P137 (P = 0.0876);.;.;.;.;.;.;.;.;.;.;.;

MVP

0.11

MPC

0.56

ClinPred

0.96

GERP RS

4.2

Varity_R

0.31

gMVP

0.75

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