rs1478241336

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006602.4(TCFL5):c.482G>T(p.Gly161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000771 in 1,037,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

TCFL5
NM_006602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

Publications

0 publications found

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:

ENSG00000302953 (HGNC:):

ENSG00000302953 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14877442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCFL5	NM_006602.4 link	c.482G>T	p.Gly161Val	missense_variant	Exon 1 of 6	ENST00000335351.8	NP_006593.2	Q9UL49-3Q86TP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCFL5	ENST00000335351.8 link	c.482G>T	p.Gly161Val	missense_variant	Exon 1 of 6	1	NM_006602.4	ENSP00000334294.3	Q9UL49-3
TCFL5	ENST00000217162.5 link	c.338G>T	p.Gly113Val	missense_variant	Exon 1 of 6	1		ENSP00000217162.5	F8W9A4
ENSG00000302953	ENST00000790712.1 link	n.-207C>A		upstream_gene_variant
ENSG00000302953	ENST00000790713.1 link	n.-228C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000455

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

890224

Hom.:

Cov.:

AF XY:

0.00000238

AC XY:

AN XY:

420372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16606

American (AMR)

AF:

0.00

AC:

AN:

2572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6204

East Asian (EAS)

AF:

0.00

AC:

AN:

6074

South Asian (SAS)

AF:

0.00

AC:

AN:

19776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1874

European-Non Finnish (NFE)

AF:

0.00000623

AC:

AN:

802046

Other (OTH)

AF:

0.00

AC:

AN:

30172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000204

AC:

AN:

146854

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40862

American (AMR)

AF:

0.00

AC:

AN:

14790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000455

AC:

AN:

65974

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.482G>T (p.G161V) alteration is located in exon 1 (coding exon 1) of the TCFL5 gene. This alteration results from a G to T substitution at nucleotide position 482, causing the glycine (G) at amino acid position 161 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.41

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PhyloP100

0.21

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.040

Sift

Benign

0.031

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.91

P;D

Vest4

0.097

MutPred

0.28

Loss of catalytic residue at G161 (P = 0.0246);.;

MVP

0.068

MPC

1.6

ClinPred

0.61

GERP RS

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.15

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over