Variant rs17854409 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006602.4(TCFL5):c.814A>G(p.Asn272Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,608,502 control chromosomes in the GnomAD database, including 6,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1316 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5444 hom. )

Consequence

TCFL5
NM_006602.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.52

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.484423E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCFL5	NM_006602.4 linkuse as main transcript	c.814A>G	p.Asn272Asp	missense_variant	2/6	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.814A>G	p.Asn272Asp	missense_variant	2/6	1	NM_006602.4	ENSP00000334294.3		Q9UL49-3
TCFL5	ENST00000217162.5 linkuse as main transcript	c.670A>G	p.Asn224Asp	missense_variant	2/6	1		ENSP00000217162.5		F8W9A4

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17794

AN:

152154

Hom.:

1316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0867

Gnomad ASJ

AF:

0.0945

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.0658

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0823

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.0894

AC:

22422

AN:

250922

Hom.:

1267

AF XY:

0.0873

AC XY:

11844

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.0495

Gnomad ASJ exome

AF:

0.0988

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.0719

Gnomad FIN exome

AF:

0.0642

Gnomad NFE exome

AF:

0.0833

Gnomad OTH exome

AF:

0.0909

GnomAD4 exome

AF:

0.0802

AC:

116759

AN:

1456230

Hom.:

5444

Cov.:

AF XY:

0.0801

AC XY:

57969

AN XY:

723368

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.0524

Gnomad4 ASJ exome

AF:

0.0983

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0739

Gnomad4 FIN exome

AF:

0.0670

Gnomad4 NFE exome

AF:

0.0761

Gnomad4 OTH exome

AF:

0.0933

GnomAD4 genome

AF:

0.117

AC:

17817

AN:

152272

Hom.:

1316

Cov.:

AF XY:

0.114

AC XY:

8498

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.0866

Gnomad4 ASJ

AF:

0.0945

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0829

Gnomad4 FIN

AF:

0.0658

Gnomad4 NFE

AF:

0.0823

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.0849

Hom.:

704

Bravo

AF:

0.123

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0724

AC:

279

ESP6500AA

AF:

0.199

AC:

878

ESP6500EA

AF:

0.0841

AC:

723

ExAC

AF:

0.0930

AC:

11294

Asia WGS

AF:

0.124

AC:

432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.00085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.11

Sift

Benign

0.082

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.43

B;B

Vest4

0.18

MPC

0.0084

ClinPred

0.0080

GERP RS

3.6

Varity_R

0.074

gMVP

0.097

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over