chr20-62860190-T-A

Variant names:

• chr20-62860190-T-A
• rs1322206793
• NM_006602.4:c.766A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006602.4(TCFL5):​c.766A>T​(p.Thr256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. T256A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• 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: 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=0.1687102).

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.766A>T	p.Thr256Ser	missense	Exon 2 of 6	NP_006593.2
	TCFL5	NM_001301726.2		c.766A>T	p.Thr256Ser	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.766A>T	p.Thr256Ser	missense	Exon 2 of 6	ENSP00000334294.3	Q9UL49-3
	TCFL5	ENST00000217162.5	TSL:1	c.622A>T	p.Thr208Ser	missense	Exon 2 of 6	ENSP00000217162.5	F8W9A4
	TCFL5	ENST00000895007.1		c.766A>T	p.Thr256Ser	missense	Exon 2 of 6	ENSP00000565066.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251190 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.089	T
Sift4G	Benign	0.19	T
Polyphen		0.61	P
Vest4		0.29
MutPred		0.14		Gain of sheet (P = 0.0827)
MVP		0.19
MPC		0.0087
ClinPred		0.34	T
GERP RS		4.7
Varity_R		0.13
gMVP		0.19
Mutation Taster		=91/9	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: rs1322206793; hg19: chr20-61491542;