Variant 16-68122320-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_173165.3(NFATC3):c.437G>C(p.Arg146Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NFATC3
NM_173165.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.51

Variant links:

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 links:

NFATC3 (HGNC:):

NFATC3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC3	NM_173165.3 linkuse as main transcript	c.437G>C	p.Arg146Thr	missense_variant	2/10	ENST00000346183.8	NP_775188.1	Q12968-1B5B2S1
NFATC3	NM_004555.4 linkuse as main transcript	c.437G>C	p.Arg146Thr	missense_variant	2/11		NP_004546.1	Q12968-2B5B2S0
NFATC3	NM_173163.3 linkuse as main transcript	c.437G>C	p.Arg146Thr	missense_variant	2/11		NP_775186.1	Q12968-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC3	ENST00000346183.8 linkuse as main transcript	c.437G>C	p.Arg146Thr	missense_variant	2/10	1	NM_173165.3	ENSP00000300659.5		Q12968-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251286

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135818

show subpopulations

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 SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.437G>C (p.R146T) alteration is located in exon 2 (coding exon 2) of the NFATC3 gene. This alteration results from a G to C substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.18

.;.;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.0

.;L;L;L

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

.;N;N;N

REVEL

Uncertain

0.43

Sift

Benign

0.17

.;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

1.0, 0.99

.;D;D;.

Vest4

0.76

MutPred

0.22

Gain of phosphorylation at R146 (P = 0.0166);Gain of phosphorylation at R146 (P = 0.0166);Gain of phosphorylation at R146 (P = 0.0166);Gain of phosphorylation at R146 (P = 0.0166);

MVP

0.47

MPC

0.51

ClinPred

0.32

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over