rs918918782

Variant names:

• chr20-62861034-C-A
• rs918918782
• NM_006602.4:c.637G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-62861034-C-A
• chr20-62861034-C-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.637G>T​(p.Ala213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 845,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A213T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: TCFL5 NM_006602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• 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=0.091367185).

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.637G>T	p.Ala213Ser	missense	Exon 1 of 6	NP_006593.2
	TCFL5	NM_001301726.2		c.637G>T	p.Ala213Ser	missense	Exon 1 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.637G>T	p.Ala213Ser	missense	Exon 1 of 6	ENSP00000334294.3	Q9UL49-3
	TCFL5	ENST00000217162.5	TSL:1	c.493G>T	p.Ala165Ser	missense	Exon 1 of 6	ENSP00000217162.5	F8W9A4
	TCFL5	ENST00000895007.1		c.637G>T	p.Ala213Ser	missense	Exon 1 of 6	ENSP00000565066.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 845990 Hom.: 0 Cov.: 31 AF XY: 0.00000255 AC XY: 1 AN XY: 392052

African (AFR) AF: 0.00 AC: 0 AN: 15976

American (AMR) AF: 0.00 AC: 0 AN: 1418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5422

East Asian (EAS) AF: 0.00 AC: 0 AN: 3968

South Asian (SAS) AF: 0.00 AC: 0 AN: 17364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1662

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 770520

Other (OTH) AF: 0.00 AC: 0 AN: 28040

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	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.062
Sift	Benign	0.10	T
Sift4G	Benign	0.096	T
Polyphen		0.24	B
Vest4		0.26
MutPred		0.16		Loss of helix (P = 0.0123)
MVP		0.082
MPC		1.3
ClinPred		0.11	T
GERP RS		-2.1
Varity_R		0.082
gMVP		0.11
Mutation Taster		=98/2	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: rs918918782; hg19: chr20-61492386;