12-51118703-G-C

Variant names:

• chr12-51118703-G-C
• ENST00000548108.1:c.-103C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000548108.1(TFCP2):​c.-103C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFCP2 ENST00000548108.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.452

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28987396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFCP2	NM_005653.5	c.192C>G	p.Ile64Met	missense_variant	Exon 2 of 15	ENST00000257915.10	NP_005644.2
TFCP2	NM_001173452.2	c.192C>G	p.Ile64Met	missense_variant	Exon 2 of 15		NP_001166923.1
TFCP2	NM_001173453.2	c.192C>G	p.Ile64Met	missense_variant	Exon 2 of 14		NP_001166924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFCP2	ENST00000257915.10	c.192C>G	p.Ile64Met	missense_variant	Exon 2 of 15	1	NM_005653.5	ENSP00000257915.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.192C>G (p.I64M) alteration is located in exon 2 (coding exon 2) of the TFCP2 gene. This alteration results from a C to G substitution at nucleotide position 192, causing the isoleucine (I) at amino acid position 64 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;.
Eigen	Benign	0.056
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.020	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.84	P;P;D
Vest4		0.26
MutPred		0.48		Gain of catalytic residue at Y69 (P = 0.0123);Gain of catalytic residue at Y69 (P = 0.0123);Gain of catalytic residue at Y69 (P = 0.0123);
MVP		0.72
MPC		1.2
ClinPred		0.38	T
GERP RS		2.8
Varity_R		0.092
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-51512486;