Genetic Variant TCF24:p.Arg49Gln (chr8-66961620-C-T) – 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.146G>A(p.Arg49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,277,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. R49W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

TCF24
NM_001193502.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

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:

Genome browser will be placed here

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=0.1896058).

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.146G>A	p.Arg49Gln	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.146G>A	p.Arg49Gln	missense	Exon 3 of 4	ENSP00000455444.1	Q7RTU0
TCF24	ENST00000929798.1		c.146G>A	p.Arg49Gln	missense	Exon 2 of 3	ENSP00000599857.1
TCF24	ENST00000929799.1		c.146G>A	p.Arg49Gln	missense	Exon 2 of 3	ENSP00000599858.1

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.87e-7

AC:

AN:

1127290

Hom.:

Cov.:

AF XY:

0.00000185

AC XY:

AN XY:

541868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23682

American (AMR)

AF:

0.00

AC:

AN:

11562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15710

East Asian (EAS)

AF:

0.00

AC:

AN:

26656

South Asian (SAS)

AF:

0.00

AC:

AN:

30708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3128

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

947118

Other (OTH)

AF:

0.00

AC:

AN:

45272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149772

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73048

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41180

American (AMR)

AF:

0.00

AC:

AN:

15040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67264

Other (OTH)

AF:

0.00

AC:

AN:

2054

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

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.028

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.19

MutationAssessor

Benign

0.90

PhyloP100

3.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.55

Sift

Benign

0.19

Sift4G

Benign

0.24

Vest4

0.12

MVP

0.77

GERP RS

4.7

Varity_R

0.15

gMVP

0.52

Mutation Taster

=75/25

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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