16-68122760-C-A

Position:

• chr16-68122760-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173165.3(NFATC3):​c.877C>A​(p.Pro293Thr) variant causes a missense change involving the alteration of a 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: 31)
• Consequence: NFATC3 NM_173165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

NFATC3 (HGNC:7777): (nuclear factor of activated T cells 3) The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]

NFATC3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC3	NM_173165.3	c.877C>A	p.Pro293Thr	missense_variant	2/10	ENST00000346183.8	NP_775188.1
NFATC3	NM_004555.4	c.877C>A	p.Pro293Thr	missense_variant	2/11		NP_004546.1
NFATC3	NM_173163.3	c.877C>A	p.Pro293Thr	missense_variant	2/11		NP_775186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC3	ENST00000346183.8	c.877C>A	p.Pro293Thr	missense_variant	2/10	1	NM_173165.3	ENSP00000300659.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.877C>A (p.P293T) alteration is located in exon 2 (coding exon 2) of the NFATC3 gene. This alteration results from a C to A substitution at nucleotide position 877, causing the proline (P) at amino acid position 293 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	.;.;D;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.1	.;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.69
MutPred		0.23		Gain of phosphorylation at P293 (P = 0.0264);Gain of phosphorylation at P293 (P = 0.0264);Gain of phosphorylation at P293 (P = 0.0264);Gain of phosphorylation at P293 (P = 0.0264);
MVP		0.32
MPC		0.45
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.38

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: chr16-68156663;