rs763849039

Variant names:

• chr20-62857536-C-T
• rs763849039
• NM_006602.4:c.1097G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006602.4(TCFL5):​c.1097G>A​(p.Gly366Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,880 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: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2896279).

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.1097G>A	p.Gly366Asp	missense	Exon 4 of 6	NP_006593.2
	TCFL5	NM_001301726.2		c.1094G>A	p.Gly365Asp	missense	Exon 4 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.1097G>A	p.Gly366Asp	missense	Exon 4 of 6	ENSP00000334294.3	Q9UL49-3
	TCFL5	ENST00000217162.5	TSL:1	c.953G>A	p.Gly318Asp	missense	Exon 4 of 6	ENSP00000217162.5	F8W9A4
	TCFL5	ENST00000895007.1		c.1094G>A	p.Gly365Asp	missense	Exon 4 of 6	ENSP00000565066.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251484 AF XY: 0.00000736

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: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.000223 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.10
Sift	Benign	0.046	D
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.23		Loss of helix (P = 0.0558)
MVP		0.35
MPC		2.1
ClinPred		0.92	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.26
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs763849039; hg19: chr20-61488888;