Genetic Variant NM_001193502.2:c.119G>C (chr8-66961647-C-G) – 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.119G>C(p.Gly40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,202,124 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G40E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TCF24
NM_001193502.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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=0.06874913).

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.119G>C	p.Gly40Ala	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.119G>C	p.Gly40Ala	missense	Exon 3 of 4	ENSP00000455444.1	Q7RTU0
TCF24	ENST00000929798.1		c.119G>C	p.Gly40Ala	missense	Exon 2 of 3	ENSP00000599857.1
TCF24	ENST00000929799.1		c.119G>C	p.Gly40Ala	missense	Exon 2 of 3	ENSP00000599858.1

Frequencies

GnomAD3 genomes

AF:

0.0000673

AC:

AN:

148612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000669

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00120

AC:

AN:

830

AF XY:

0.00204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

131

AN:

1053512

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

501038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21362

American (AMR)

AF:

0.000980

AC:

AN:

7144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12452

East Asian (EAS)

AF:

0.00

AC:

AN:

22750

South Asian (SAS)

AF:

0.00

AC:

AN:

21456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2728

European-Non Finnish (NFE)

AF:

0.000130

AC:

118

AN:

904812

Other (OTH)

AF:

0.000147

AC:

AN:

40938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000673

AC:

AN:

148612

Hom.:

Cov.:

AF XY:

0.0000829

AC XY:

AN XY:

72380

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41082

American (AMR)

AF:

0.0000669

AC:

AN:

14946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000109

AC:

AN:

9158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000105

AC:

AN:

66754

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000132

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

0.075

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.069

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.0

Sift

Benign

0.56

Sift4G

Benign

0.95

Vest4

0.19

MVP

0.82

GERP RS

3.7

Varity_R

0.086

gMVP

0.38

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over