20-62859507-G-C

Variant names:

• chr20-62859507-G-C
• rs1313428058
• NM_006602.4:c.851C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006602.4(TCFL5):​c.851C>G​(p.Ser284Cys) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2602094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCFL5	NM_006602.4	c.851C>G	p.Ser284Cys	missense_variant	Exon 3 of 6	ENST00000335351.8	NP_006593.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCFL5	ENST00000335351.8	c.851C>G	p.Ser284Cys	missense_variant	Exon 3 of 6	1	NM_006602.4	ENSP00000334294.3
TCFL5	ENST00000217162.5	c.707C>G	p.Ser236Cys	missense_variant	Exon 3 of 6	1		ENSP00000217162.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.851C>G (p.S284C) alteration is located in exon 3 (coding exon 3) of the TCFL5 gene. This alteration results from a C to G substitution at nucleotide position 851, causing the serine (S) at amino acid position 284 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		1.0	D;D
Vest4		0.40
MutPred		0.20		Loss of disorder (P = 0.0218);.;
MVP		0.13
MPC		0.028
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.19

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: rs1313428058; hg19: chr20-61490859;