Variant chr20-62861049-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000335351.8(TCFL5):c.622C>T(p.Pro208Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000382 in 995,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TCFL5
ENST00000335351.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

TCFL5 (HGNC:11646): (transcription factor like 5) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; regulation of cell population proliferation; and spermatogenesis. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCFL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0625774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCFL5	NM_006602.4 linkuse as main transcript	c.622C>T	p.Pro208Ser	missense_variant	1/6	ENST00000335351.8	NP_006593.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCFL5	ENST00000335351.8 linkuse as main transcript	c.622C>T	p.Pro208Ser	missense_variant	1/6	1	NM_006602.4	ENSP00000334294	A2	Q9UL49-3
TCFL5	ENST00000217162.5 linkuse as main transcript	c.478C>T	p.Pro160Ser	missense_variant	1/6	1		ENSP00000217162	P4

Frequencies

GnomAD3 genomes

AF:

0.000163

AC:

AN:

147442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000587

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

847568

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

393050

show subpopulations

Gnomad4 AFR exome

AF:

0.000875

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

AF:

0.000163

AC:

AN:

147546

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

71888

show subpopulations

Gnomad4 AFR

AF:

0.000585

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000185

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

May 26, 2023

The c.622C>T (p.P208S) alteration is located in exon 1 (coding exon 1) of the TCFL5 gene. This alteration results from a C to T substitution at nucleotide position 622, causing the proline (P) at amino acid position 208 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

0.067

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0051

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.44

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.024

Sift

Benign

0.58

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.020

B;B

Vest4

0.079

MutPred

0.29

Gain of phosphorylation at P208 (P = 0.0108);.;

MVP

0.068

MPC

1.4

ClinPred

0.25

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.026

gMVP

0.12

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