20-62861045-T-A

Position:

• chr20-62861045-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006602.4(TCFL5):​c.626A>T​(p.Glu209Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000118 in 847,034 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: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

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 (HGNC:):

ACMG classification

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=0.32320726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCFL5	NM_006602.4	c.626A>T	p.Glu209Val	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	c.626A>T	p.Glu209Val	missense_variant	1/6	1	NM_006602.4	ENSP00000334294.3
TCFL5	ENST00000217162.5	c.482A>T	p.Glu161Val	missense_variant	1/6	1		ENSP00000217162.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 847034 Hom.: 0 Cov.: 31 AF XY: 0.00000255 AC XY: 1 AN XY: 392732

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: 0.00000130

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.626A>T (p.E209V) alteration is located in exon 1 (coding exon 1) of the TCFL5 gene. This alteration results from a A to T substitution at nucleotide position 626, causing the glutamic acid (E) at amino acid position 209 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	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.48	T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.085
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.97	D;D
Vest4		0.46
MutPred		0.19		Loss of solvent accessibility (P = 0.0146);.;
MVP		0.068
MPC		2.0
ClinPred		0.93	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.27
gMVP		0.38

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.

Other links and lift over

hg19: chr20-61492397;