Variant 20-62861118-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006602.4(TCFL5):c.553G>C(p.Val185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000801 in 998,898 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: 𝑓 0.000095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

TCFL5
NM_006602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

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:

TCFL5 (HGNC:):

TCFL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35654435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCFL5	NM_006602.4 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	1/6	ENST00000335351.8	NP_006593.2	Q9UL49-3Q86TP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCFL5	ENST00000335351.8 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	1/6	1	NM_006602.4	ENSP00000334294.3		Q9UL49-3
TCFL5	ENST00000217162.5 linkuse as main transcript	c.409G>C	p.Val137Leu	missense_variant	1/6	1		ENSP00000217162.5		F8W9A4

Frequencies

GnomAD3 genomes

AF:

0.0000954

AC:

AN:

146750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

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:

0.000585

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000121

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000775

AC:

AN:

852148

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

395734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000826

Gnomad4 OTH exome

AF:

0.0000705

GnomAD4 genome

AF:

0.0000954

AC:

AN:

146750

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71392

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000585

Gnomad4 NFE

AF:

0.000121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000378

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

Jan 04, 2022

The c.553G>C (p.V185L) alteration is located in exon 1 (coding exon 1) of the TCFL5 gene. This alteration results from a G to C substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by a leucine (L). 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.053

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

T;T

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.1

L;.

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.063

Sift

Uncertain

0.029

D;D

Sift4G

Benign

0.17

T;D

Polyphen

0.95

P;D

Vest4

0.50

MutPred

0.22

Loss of sheet (P = 0.0104);.;

MVP

0.20

MPC

2.6

ClinPred

0.73

GERP RS

2.8

Varity_R

0.16

gMVP

0.24

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