chr12-51103696-A-G

Variant names:

• chr12-51103696-A-G
• NM_005653.5:c.1034T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005653.5(TFCP2):​c.1034T>C​(p.Phe345Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFCP2 NM_005653.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71
• Publications: 0 publications found

Genes affected

TFCP2 (HGNC:11748): (transcription factor CP2) This gene encodes a transcription factor that binds the alpha-globin promoter and activates transcription of the alpha-globin gene. The encoded protein regulates erythroid gene expression, plays a role in the transcriptional switch of globin gene promoters, and it activates many other cellular and viral gene promoters. The gene product interacts with certain inflammatory response factors, and polymorphisms of this gene may be involved in the pathogenesis of Alzheimer's disease. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005653.5. 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
	TFCP2	NM_005653.5	MANE Select	c.1034T>C	p.Phe345Ser	missense	Exon 10 of 15	NP_005644.2
	TFCP2	NM_001173452.2		c.1034T>C	p.Phe345Ser	missense	Exon 10 of 15	NP_001166923.1	Q12800-4
	TFCP2	NM_001173453.2		c.881T>C	p.Phe294Ser	missense	Exon 9 of 14	NP_001166924.1	Q12800-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFCP2	ENST00000257915.10	TSL:1 MANE Select	c.1034T>C	p.Phe345Ser	missense	Exon 10 of 15	ENSP00000257915.5	Q12800-1
	TFCP2	ENST00000548108.1	TSL:1	c.740T>C	p.Phe247Ser	missense	Exon 10 of 14	ENSP00000449280.1	F8VWL0
	TFCP2	ENST00000930488.1		c.1181T>C	p.Phe394Ser	missense	Exon 11 of 16	ENSP00000600547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.95
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.028	D
Polyphen		0.33	B
Vest4		0.60
MutPred		0.53		Gain of catalytic residue at R341 (P = 0.001)
MVP		0.72
MPC		1.5
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.90
Mutation Taster		=38/62	disease causing

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

hg19: chr12-51497479;