20-62860142-T-C

Variant names:

• chr20-62860142-T-C
• rs17854409
• NM_006602.4:c.814A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N272Y) has been classified as Uncertain significance.

• 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
• Publications: 27 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: Benign. The variant received -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.

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.814A>G	p.Asn272Asp	missense	Exon 2 of 6	NP_006593.2
	TCFL5	NM_001301726.2		c.814A>G	p.Asn272Asp	missense	Exon 2 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.814A>G	p.Asn272Asp	missense	Exon 2 of 6	ENSP00000334294.3	Q9UL49-3
	TCFL5	ENST00000217162.5	TSL:1	c.670A>G	p.Asn224Asp	missense	Exon 2 of 6	ENSP00000217162.5	F8W9A4
	TCFL5	ENST00000895007.1		c.814A>G	p.Asn272Asp	missense	Exon 2 of 6	ENSP00000565066.1

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

GnomAD2 exomes AF: 0.0894 AC: 22422 AN: 250922 AF XY: 0.0873

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 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

African (AFR) AF: 0.211 AC: 7042 AN: 33398

American (AMR) AF: 0.0524 AC: 2338 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 2562 AN: 26056

East Asian (EAS) AF: 0.104 AC: 4104 AN: 39540

South Asian (SAS) AF: 0.0739 AC: 6366 AN: 86088

European-Finnish (FIN) AF: 0.0670 AC: 3574 AN: 53372

Middle Eastern (MID) AF: 0.150 AC: 855 AN: 5688

European-Non Finnish (NFE) AF: 0.0761 AC: 84307 AN: 1107316

Other (OTH) AF: 0.0933 AC: 5611 AN: 60134

GnomAD4 genome AF: 0.117 AC: 17817 AN: 152272 Hom.: 1316 Cov.: 32 AF XY: 0.114 AC XY: 8498 AN XY: 74462

African (AFR) AF: 0.201 AC: 8341 AN: 41518

American (AMR) AF: 0.0866 AC: 1325 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.145 AC: 753 AN: 5188

South Asian (SAS) AF: 0.0829 AC: 400 AN: 4824

European-Finnish (FIN) AF: 0.0658 AC: 699 AN: 10618

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5597 AN: 68026

Other (OTH) AF: 0.123 AC: 259 AN: 2114

Alfa AF: 0.0919 Hom.: 2029

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 v4.9

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
MetaRNN	Benign	0.00085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.082	T
Sift4G	Benign	0.10	T
Polyphen		0.43	B
Vest4		0.18
MPC		0.0084
ClinPred		0.0080	T
GERP RS		3.6
Varity_R		0.074
gMVP		0.097
Mutation Taster		=99/1	polymorphism (auto)

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