rs1573402593

Variant names:

• chr2-121281174-C-G
• rs1573402593
• NM_014553.3:c.160G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-121281174-C-G
• chr2-121281174-C-T

Variant summary

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

The NM_014553.3(TFCP2L1):​c.160G>C​(p.Ala54Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TFCP2L1 NM_014553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

Genes affected

TFCP2L1 (HGNC:17925): (transcription factor CP2 like 1) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and membrane. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFCP2L1	NM_014553.3	c.160G>C	p.Ala54Pro	missense_variant	Exon 2 of 15	ENST00000263707.6	NP_055368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFCP2L1	ENST00000263707.6	c.160G>C	p.Ala54Pro	missense_variant	Exon 2 of 15	1	NM_014553.3	ENSP00000263707.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160G>C (p.A54P) alteration is located in exon 2 (coding exon 2) of the TFCP2L1 gene. This alteration results from a G to C substitution at nucleotide position 160, causing the alanine (A) at amino acid position 54 to be replaced by a proline (P). 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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.17
Sift	Benign	0.19	T
Sift4G	Benign	0.24	T
Polyphen		0.35	B
Vest4		0.72
MutPred		0.67		Loss of sheet (P = 0.0315);
MVP		0.17
MPC		0.66
ClinPred		0.90	D
GERP RS		2.3
Varity_R		0.54
gMVP		0.69
Mutation Taster		=51/49	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

Publications

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Other links and lift over

dbSNP: rs1573402593; hg19: chr2-122038750;