NM_004609.4:c.463G>C

Variant names:

• chr20-609775-C-G
• rs1354210845
• NM_004609.4:c.463G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004609.4(TCF15):​c.463G>C​(p.Ala155Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCF15 NM_004609.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057062566).
• BP6: Variant 20-609775-C-G is Benign according to our data. Variant chr20-609775-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2534667.Status of the report is criteria_provided_single_submitter, 1 stars.

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.463G>C	p.Ala155Pro	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.463G>C	p.Ala155Pro	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: 1259962 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 618822

African (AFR) AF: 0.00 AC: 0 AN: 24976

American (AMR) AF: 0.00 AC: 0 AN: 13656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19126

East Asian (EAS) AF: 0.00 AC: 0 AN: 28018

South Asian (SAS) AF: 0.00 AC: 0 AN: 59148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028260

Other (OTH) AF: 0.00 AC: 0 AN: 51970

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.057
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	8.5
DANN	Benign	0.97
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.23
Sift	Benign	0.38	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.34		Loss of stability (P = 0.0216)
MVP		0.15
MPC		1.5
ClinPred		0.10	T
GERP RS		-1.2
Varity_R		0.059
gMVP		0.23
Mutation Taster		=94/6	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: rs1354210845; hg19: chr20-590419;