chr20-610111-C-A

Variant names:

• chr20-610111-C-A
• NM_004609.4:c.127G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004609.4(TCF15):​c.127G>T​(p.Gly43Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCF15 NM_004609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.127G>T	p.Gly43Cys	missense	Exon 1 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.127G>T	p.Gly43Cys	missense	Exon 1 of 2	ENSP00000246080.3	Q12870

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 860740 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 402920

African (AFR) AF: 0.00 AC: 0 AN: 16266

American (AMR) AF: 0.00 AC: 0 AN: 3104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4104

South Asian (SAS) AF: 0.00 AC: 0 AN: 22264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 776558

Other (OTH) AF: 0.00 AC: 0 AN: 28424

GnomAD4 genome Cov.: 32

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	Benign	0.20
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Benign	1.7	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.22		Gain of loop (P = 0.0312)
MVP		0.62
MPC		2.2
ClinPred		0.93	D
GERP RS		4.5
PromoterAI		-0.038	Neutral
Varity_R		0.36
gMVP		0.39
Mutation Taster		=80/20	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

hg19: chr20-590755;