chr20-604607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004609.4(TCF15):​c.584G>A​(p.Arg195Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,553,202 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TCF15
NM_004609.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3642628).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF15NM_004609.4 linkc.584G>A p.Arg195Gln missense_variant Exon 2 of 2 ENST00000246080.4 NP_004600.3 Q12870A4LBB6Q6NVX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCF15ENST00000246080.4 linkc.584G>A p.Arg195Gln missense_variant Exon 2 of 2 1 NM_004609.4 ENSP00000246080.3 Q12870

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000127
AC:
2
AN:
157634
Hom.:
0
AF XY:
0.0000120
AC XY:
1
AN XY:
83542
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000873
Gnomad SAS exome
AF:
0.0000437
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000114
AC:
16
AN:
1401064
Hom.:
0
Cov.:
30
AF XY:
0.0000130
AC XY:
9
AN XY:
691268
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000119
Gnomad4 EAS exome
AF:
0.0000558
Gnomad4 SAS exome
AF:
0.0000378
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000463
Gnomad4 OTH exome
AF:
0.0000344
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000946
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.584G>A (p.R195Q) alteration is located in exon 2 (coding exon 2) of the TCF15 gene. This alteration results from a G to A substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a glutamine (Q). 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
0.17
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
0.64
D
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.89
N
REVEL
Uncertain
0.54
Sift
Benign
0.076
T
Sift4G
Benign
0.096
T
Polyphen
1.0
D
Vest4
0.27
MutPred
0.36
Loss of methylation at R195 (P = 0.0143);
MVP
0.74
MPC
2.0
ClinPred
0.63
D
GERP RS
4.1
Varity_R
0.21
gMVP
0.50

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755340067; hg19: chr20-585251; API