chr20-62861034-C-T

Variant names:

• chr20-62861034-C-T
• rs918918782
• NM_006602.4:c.637G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006602.4(TCFL5):​c.637G>A​(p.Ala213Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 994,448 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 0.000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051362872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006602.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCFL5	NM_006602.4	MANE Select	c.637G>A	p.Ala213Thr	missense	Exon 1 of 6	NP_006593.2
	TCFL5	NM_001301726.2		c.637G>A	p.Ala213Thr	missense	Exon 1 of 6	NP_001288655.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCFL5	ENST00000335351.8	TSL:1 MANE Select	c.637G>A	p.Ala213Thr	missense	Exon 1 of 6	ENSP00000334294.3	Q9UL49-3
	TCFL5	ENST00000217162.5	TSL:1	c.493G>A	p.Ala165Thr	missense	Exon 1 of 6	ENSP00000217162.5	F8W9A4
	TCFL5	ENST00000895007.1		c.637G>A	p.Ala213Thr	missense	Exon 1 of 6	ENSP00000565066.1

Frequencies

GnomAD3 genomes AF: 0.0000674 AC: 10 AN: 148458 Hom.: 0 Cov.: 32

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: 0.000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 64 AF XY: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 121 AN: 845990 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 63 AN XY: 392052

African (AFR) AF: 0.00 AC: 0 AN: 15976

American (AMR) AF: 0.00 AC: 0 AN: 1418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5422

East Asian (EAS) AF: 0.00 AC: 0 AN: 3968

South Asian (SAS) AF: 0.000346 AC: 6 AN: 17364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1620

Middle Eastern (MID) AF: 0.000602 AC: 1 AN: 1662

European-Non Finnish (NFE) AF: 0.000143 AC: 110 AN: 770520

Other (OTH) AF: 0.000143 AC: 4 AN: 28040

GnomAD4 genome AF: 0.0000674 AC: 10 AN: 148458 Hom.: 0 Cov.: 32 AF XY: 0.0000553 AC XY: 4 AN XY: 72310

African (AFR) AF: 0.00 AC: 0 AN: 41064

American (AMR) AF: 0.00 AC: 0 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000150 AC: 10 AN: 66676

Other (OTH) AF: 0.00 AC: 0 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.054
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.14
MutPred		0.18		Gain of glycosylation at A213 (P = 0.0126)
MVP		0.068
MPC		1.3
ClinPred		0.070	T
GERP RS		-2.1
Varity_R		0.061
gMVP		0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs918918782; hg19: chr20-61492386;