Genetic Variant TCF24:p.Pro17Ser (chr8-66961717-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001193502.2(TCF24):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000454 in 1,101,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

TCF24
NM_001193502.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.543

Publications

0 publications found

Variant links:

Genes affected

TCF24 (HGNC:32275): (transcription factor 24) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in developmental process and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCF24 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0960843).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193502.2. 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
	TCF24	NM_001193502.2	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 3 of 4	NP_001180431.1	Q7RTU0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF24	ENST00000563496.2	TSL:5 MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 3 of 4	ENSP00000455444.1	Q7RTU0
TCF24	ENST00000929798.1		c.49C>T	p.Pro17Ser	missense	Exon 2 of 3	ENSP00000599857.1
TCF24	ENST00000929799.1		c.49C>T	p.Pro17Ser	missense	Exon 2 of 3	ENSP00000599858.1

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000420

AC:

AN:

951342

Hom.:

Cov.:

AF XY:

0.00000448

AC XY:

AN XY:

446168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18726

American (AMR)

AF:

0.00

AC:

AN:

4292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9046

East Asian (EAS)

AF:

0.00

AC:

AN:

14848

South Asian (SAS)

AF:

0.00

AC:

AN:

18050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2258

European-Non Finnish (NFE)

AF:

0.00000477

AC:

AN:

837886

Other (OTH)

AF:

0.00

AC:

AN:

34628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149722

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41156

American (AMR)

AF:

0.00

AC:

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67288

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0052

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.096

MutationAssessor

Benign

0.34

PhyloP100

0.54

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.32

Sift

Benign

0.11

Sift4G

Benign

0.17

Vest4

0.070

MVP

0.77

GERP RS

0.44

Varity_R

0.028

gMVP

0.54

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over