20-62860142-T-C

Position:

• chr20-62860142-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

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 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	c.814A>G	p.Asn272Asp	missense_variant	2/6	ENST00000335351.8	NP_006593.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCFL5	ENST00000335351.8	c.814A>G	p.Asn272Asp	missense_variant	2/6	1	NM_006602.4	ENSP00000334294.3
TCFL5	ENST00000217162.5	c.670A>G	p.Asn224Asp	missense_variant	2/6	1		ENSP00000217162.5

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17794 AN: 152154 Hom.: 1316 Cov.: 32

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

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.: 31 AF XY: 0.0801 AC XY: 57969 AN XY: 723368

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.: 32 AF XY: 0.114 AC XY: 8498 AN XY: 74462

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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.38	T;T
MetaRNN	Benign	0.00085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs17854409; hg19: chr20-61491494; COSMIC: COSV53897543;