20-604625-C-T

Variant names:

• chr20-604625-C-T
• rs199584509
• NM_004609.4:c.566G>A

Variant summary

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

The NM_004609.4(TCF15):​c.566G>A​(p.Arg189Lys) 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. 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. R189M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCF15 NM_004609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 1 publications found

Genes affected

TCF15 (HGNC:11627): (transcription factor 15) The protein encoded by this gene is found in the nucleus and may be involved in the early transcriptional regulation of patterning of the mesoderm. The encoded basic helix-loop-helix protein requires dimerization with another basic helix-loop-helix protein for efficient DNA binding. [provided by RefSeq, Jul 2008]

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=0.3397945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004609.4. 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
	TCF15	NM_004609.4	MANE Select	c.566G>A	p.Arg189Lys	missense	Exon 2 of 2	NP_004600.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF15	ENST00000246080.4	TSL:1 MANE Select	c.566G>A	p.Arg189Lys	missense	Exon 2 of 2	ENSP00000246080.3	Q12870

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.61	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.47
Sift	Benign	0.033	D
Sift4G	Benign	0.086	T
Polyphen		0.88	P
Vest4		0.33
MutPred		0.46		Gain of solvent accessibility (P = 0.0022)
MVP		0.73
MPC		1.8
ClinPred		0.88	D
GERP RS		5.1
Varity_R		0.44
gMVP		0.57
Mutation Taster		=71/29	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: rs199584509; hg19: chr20-585269;