Genetic Variant NM_001193502.2:c.100C>T (chr8-66961666-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001193502.2(TCF24):c.100C>T(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000782 in 1,112,916 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

TCF24
NM_001193502.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.083417624).

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.100C>T	p.Pro34Ser	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.100C>T	p.Pro34Ser	missense	Exon 3 of 4	ENSP00000455444.1	Q7RTU0
TCF24	ENST00000929798.1		c.100C>T	p.Pro34Ser	missense	Exon 2 of 3	ENSP00000599857.1
TCF24	ENST00000929799.1		c.100C>T	p.Pro34Ser	missense	Exon 2 of 3	ENSP00000599858.1

Frequencies

GnomAD3 genomes

AF:

0.0000607

AC:

AN:

148306

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:

0.00155

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000809

AC:

AN:

964504

Hom.:

Cov.:

AF XY:

0.0000750

AC XY:

AN XY:

453144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19132

American (AMR)

AF:

0.00

AC:

AN:

4862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9466

East Asian (EAS)

AF:

0.00545

AC:

AN:

14300

South Asian (SAS)

AF:

0.00

AC:

AN:

18496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

846676

Other (OTH)

AF:

0.00

AC:

AN:

35544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.584

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:

0.0000606

AC:

AN:

148412

Hom.:

Cov.:

AF XY:

0.0000691

AC XY:

AN XY:

72320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41168

American (AMR)

AF:

0.00

AC:

AN:

14952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00155

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66562

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

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:

0.0000756

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

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

5.7

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.083

MutationAssessor

Benign

0.34

PhyloP100

-0.14

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.27

Sift

Benign

0.082

Sift4G

Benign

0.32

Vest4

0.086

MVP

0.77

GERP RS

0.55

Varity_R

0.024

gMVP

0.36

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over