16-89885912-G-T

Variant names:

• chr16-89885912-G-T
• rs745567962
• NM_014972.3:c.494G>T

Variant summary

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

The NM_014972.3(TCF25):​c.494G>T​(p.Arg165Leu) 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. 14/21 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. R165H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCF25 NM_014972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

TCF25 (HGNC:29181): (transcription factor 25) TCF25 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that are important in embryonic development (Steen and Lindholm, 2008 [PubMed 18068114]).[supplied by OMIM, Sep 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060661554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014972.3. 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
	TCF25	NM_014972.3	MANE Select	c.494G>T	p.Arg165Leu	missense	Exon 4 of 18	NP_055787.1	Q9BQ70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF25	ENST00000263346.13	TSL:1 MANE Select	c.494G>T	p.Arg165Leu	missense	Exon 4 of 18	ENSP00000263346.8	Q9BQ70
	TCF25	ENST00000562256.5	TSL:1	c.77G>T	p.Arg26Leu	missense	Exon 2 of 17	ENSP00000455611.1	H3BQ53
	TCF25	ENST00000856681.1		c.494G>T	p.Arg165Leu	missense	Exon 4 of 18	ENSP00000526740.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.093
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.028
Sift	Benign	0.064	T
Sift4G	Benign	0.26	T
Polyphen		0.29	B
Vest4		0.26
MutPred		0.24		Gain of glycosylation at P170 (P = 0.107)
MVP		0.12
MPC		0.19
ClinPred		0.23	T
GERP RS		-5.4
Varity_R		0.030
gMVP		0.13

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: rs745567962; hg19: chr16-89952320;