NM_001193502.2:c.235G>T

Variant names:

• chr8-66961531-C-A
• rs538845993
• NM_001193502.2:c.235G>T

Variant summary

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

The NM_001193502.2(TCF24):​c.235G>T​(p.Val79Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,358,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: TCF24 NM_001193502.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

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]

ACMG classification

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

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.235G>T	p.Val79Leu	missense	Exon 3 of 4	NP_001180431.1	Q7RTU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF24	ENST00000563496.2	TSL:5 MANE Select	c.235G>T	p.Val79Leu	missense	Exon 3 of 4	ENSP00000455444.1	Q7RTU0
	TCF24	ENST00000929798.1		c.235G>T	p.Val79Leu	missense	Exon 2 of 3	ENSP00000599857.1
	TCF24	ENST00000929799.1		c.235G>T	p.Val79Leu	missense	Exon 2 of 3	ENSP00000599858.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000479 AC: 5 AN: 104310 AF XY: 0.0000689

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000236 AC: 32 AN: 1358272 Hom.: 0 Cov.: 31 AF XY: 0.0000313 AC XY: 21 AN XY: 670090

African (AFR) AF: 0.0000357 AC: 1 AN: 28028

American (AMR) AF: 0.00 AC: 0 AN: 33282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24276

East Asian (EAS) AF: 0.00 AC: 0 AN: 31912

South Asian (SAS) AF: 0.000366 AC: 28 AN: 76524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068606

Other (OTH) AF: 0.0000528 AC: 3 AN: 56830

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000365 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.68	D
MutationAssessor	Benign	0.68	N
PhyloP100		7.8
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.0	D
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.60
MVP		0.79
GERP RS		5.2
Varity_R		0.61
gMVP		0.58
Mutation Taster		=72/28	polymorphism

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: rs538845993; hg19: chr8-67873766;